Fiscal policy under financial stress: A threshold VAR approach

The purpose of the project is to measure the impact of fiscal policy on the Portuguese GDP and how it may vary according to the state of the financial market. A Threshold VAR model is presented in which the two regimes are found using a financial stress index that divides the economy into a situation of financial stress and financial stability.

Geographic weighted regression: applicability to epidemiological studies of leprosy

Abstract: INTRODUCTION: Geographic information systems (GIS) enable public health data to be analyzed in terms of geographical variability and the relationship between risk factors and diseases. This study discusses the application of the geographic weighted regression (GWR) model to health data to improve the understanding of spatially varying social and clinical factors that potentially impact leprosy prevalence. METHODS: This ecological study used data from leprosy case records from 1998-2006, aggregated by neighborhood in the Duque de Caxias municipality in the State of Rio de Janeiro, Brazil. In the GWR model, the associations between the log of the leprosy detection rate and social and clinical factors were analyzed. RESULTS: Maps of the estimated coefficients by neighborhood confirmed the heterogeneous spatial relationships between the leprosy detection rates and the predictors. The proportion of households with piped water was associated with higher detection rates, mainly in the northeast of the municipality. Indeterminate forms were strongly associated with higher detections rates in the south, where access to health services was more established. CONCLUSIONS: GWR proved a useful tool for epidemiological analysis of leprosy in a local area, such as Duque de Caxias. Epidemiological analysis using the maps of the GWR model offered the advantage of visualizing the problem in sub-regions and identifying any spatial dependence in the local study area.

Extreme value Birnbaum-Saunders regression models applied to environmental data

Extreme value models are widely used in different areas. The Birnbaum–Saunders distribution is receiving considerable attention due to its physical arguments and its good properties. We propose a methodology based on extreme value Birnbaum–Saunders regression models, which includes model formulation, estimation, inference and checking. We further conduct a simulation study for evaluating its performance. A statistical analysis with real-world extreme value environmental data using the methodology is provided as illustration.

A VEP study in sleeping and awake one-month-old infants and its relation with social behavior

With the present study we aimed to analyze the relationship between infants' behavior and their visual evoked-potential (VEPs) response. Specifically, we want to verify differences regarding the VEP response in sleeping and awake infants and if an association between VEP components, in both groups, with neurobehavioral outcome could be identified. To do so, thirty-two full-term and healthy infants, approximately 1-month of age, were assessed through a VEP unpatterned flashlight stimuli paradigm, offered in two different intensities, and were assessed using a neurobehavioral scale. However, only 18 infants have both assessments, and therefore, these is the total included in both analysis. Infants displayed a mature neurobehavioral outcome, expected for their age. We observed that P2 and N3 components were present in both sleeping and awake infants. Differences between intensities were found regarding the P2 amplitude, but only in awake infants. Regression analysis showed that N3 amplitude predicted an adequate social interactive and internal regulatory behavior in infants who were awake during the stimuli presentation. Taking into account that social orientation and regulatory behaviors are fundamental keys for social-like behavior in 1-month-old infants, this study provides an important approach for assessing physiological biomarkers (VEPs) and its relation with social behavior, very early in postnatal development. Moreover, we evidence the importance of the infant's state when studying differences regarding visual threshold processing and its association with behavioral outcome.

Exercise and heart failure. Relation of the severity of the disease to the anaerobic threshold and the respiratory compensation point

OBJECTIVE - To identify, the anaerobic threshold and respiratory compensation point in patients with heart failure. METHODS - The study comprised 42 Men,divided according to the functional class (FC) as follows: group I (GI) - 15 patients in FC I; group II (GII) - 15 patients in FC II; and group III (GIII) - 12 patients in FC III. Patients underwent a treadmill cardiopulmonary exercise test, where the expired gases were analyzed. RESULTS - The values for the heart rate (in bpm) at the anaerobic threshold were the following: GI, 122±27; GII, 117±17; GIII, 114±22. At the respiratory compensation point, the heart rates (in bpm) were as follows: GI, 145±33; GII, 133±14; GIII 123±22. The values for the heart rates at the respiratory compensation point in GI and GIII showed statistical difference. The values of oxygen consumption (VO2) at the anaerobic threshold were the following (in ml/kg/min): GI, 13.6±3.25; GII, 10.77±1.89; GIII, 8.7±1.44 and, at the respiratory compensation point, they were as follows: GI, 19.1±2.2; GII, 14.22±2.63; GIII, 10.27±1.85. CONCLUSION - Patients with stable functional class I, II, and III heart failure reached the anaerobic threshold and the respiratory compensation point at different levels of oxygen consumption and heart rate. The role played by these thresholds in physical activity for this group of patients needs to be better clarified.

Do Diabetic Patients with Acute Coronary Syndromes Have a Higher Threshold for Ischemic Pain?

Background: Data from over 4 decades have reported a higher incidence of silent infarction among patients with diabetes mellitus (DM), but recent publications have shown conflicting results regarding the correlation between DM and presence of pain in patients with acute coronary syndromes (ACS). Objective: Our primary objective was to analyze the association between DM and precordial pain at hospital arrival. Secondary analyses evaluated the association between hyperglycemia and precordial pain at presentation, and the subgroup of patients presenting within 6 hours of symptom onset. Methods: We analyzed a prospectively designed registry of 3,544 patients with ACS admitted to a Coronary Care Unit of a tertiary hospital. We developed multivariable models to adjust for potential confounders. Results: Patients with precordial pain were less likely to have DM (30.3%) than those without pain (34.0%; unadjusted p = 0.029), but this difference was not significant after multivariable adjustment, for the global population (p = 0.84), and for subset of patients that presented within 6 hours from symptom onset (p = 0.51). In contrast, precordial pain was more likely among patients with hyperglycemia (41.2% vs 37.0% without hyperglycemia, p = 0.035) in the overall population and also among those who presented within 6 hours (41.6% vs. 32.3%, p = 0.001). Adjusted models showed an independent association between hyperglycemia and pain at presentation, especially among patients who presented within 6 hours (OR = 1.41, p = 0.008). Conclusion: In this non-selected ACS population, there was no correlation between DM and hospital presentation without precordial pain. Moreover, hyperglycemia correlated significantly with pain at presentation, especially in the population that arrived within 6 hours from symptom onset.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression

Background:Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers.Objective:To assess the association between changes in lipid markers and regression of CPV using published data.Methods:We collected data from the control, placebo and intervention arms in studies that compared the effect of lipidlowering treatments on CPV, and from the placebo and control arms in studies that tested drugs that did not affect lipids. Baseline and final measurements of plaque volume, expressed in mm3, were extracted and the percentage changes after the interventions were calculated. Performing three linear regression analyses, we assessed the relationship between percentage and absolute changes in lipid markers and percentage variations in CPV.Results:Twenty-seven studies were selected. Correlations between percentage changes in LDL-C, non-HDL-C, and apolipoprotein B (ApoB) and percentage changes in CPV were moderate (r = 0.48, r = 0.47, and r = 0.44, respectively). Correlations between absolute differences in LDL-C, non‑HDL-C, and ApoB with percentage differences in CPV were stronger (r = 0.57, r = 0.52, and r = 0.79). The linear regression model showed a statistically significant association between a reduction in lipid markers and regression of plaque volume.Conclusion:A significant association between changes in different atherogenic particles and regression of CPV was observed. The absolute reduction in ApoB showed the strongest correlation with coronary plaque regression.

Optimal designs for mixed effects poisson regression models

Magdeburg, Univ., Fak. für Mathematik, Diss., 2010

Optimal designs for the prediction in hierarchical random coefficient regression models

Magdeburg, Univ., Fak. für Mathematik, Diss., 2015

Business Cycle Regimes in CEECs Production: A Threshold SURE Approach

We use a threshold seemingly unrelated regressions specification to assess whether the Central and East European countries (CEECs) are synchronized in their business cycles to the Euro-area. This specification is useful in two ways: First, it takes into account the common institutional factors and the similarities across CEECs in their process of economic transition. Second, it captures business cycle asymmetries by allowing for the presence of two distinct regimes for the CEECs. As the CEECs are strongly affected by the Euro-area these regimes may be associated with Euro-area expansions and contractions. We discuss representation, estimation by maximum likelihood and inference. The methodology is illustrated by using monthly industrial production in 8 CEECs. The results show that apart from Lithuania the rest of the CEECs experience “normal” growth when the Euro-area contracts and “high” growth when the Euro-area expands. Given that the CEECs are “catching up” with the Euro-area this result shows that most CEECs seem synchronized to the Euro-area cycle. Keywords: Threshold SURE; asymmetry; business cycles; CEECs. JEL classification: C33; C50; E32.

A nonlinear threshold model for the dependence of extremes of stationary sequences

One of the main implications of the efficient market hypothesis (EMH) is that expected future returns on financial assets are not predictable if investors are risk neutral. In this paper we argue that financial time series offer more information than that this hypothesis seems to supply. In particular we postulate that runs of very large returns can be predictable for small time periods. In order to prove this we propose a TAR(3,1)-GARCH(1,1) model that is able to describe two different types of extreme events: a first type generated by large uncertainty regimes where runs of extremes are not predictable and a second type where extremes come from isolated dread/joy events. This model is new in the literature in nonlinear processes. Its novelty resides on two features of the model that make it different from previous TAR methodologies. The regimes are motivated by the occurrence of extreme values and the threshold variable is defined by the shock affecting the process in the preceding period. In this way this model is able to uncover dependence and clustering of extremes in high as well as in low volatility periods. This model is tested with data from General Motors stocks prices corresponding to two crises that had a substantial impact in financial markets worldwide; the Black Monday of October 1987 and September 11th, 2001. By analyzing the periods around these crises we find evidence of statistical significance of our model and thereby of predictability of extremes for September 11th but not for Black Monday. These findings support the hypotheses of a big negative event producing runs of negative returns in the first case, and of the burst of a worldwide stock market bubble in the second example. JEL classification: C12; C15; C22; C51 Keywords and Phrases: asymmetries, crises, extreme values, hypothesis testing, leverage effect, nonlinearities, threshold models

T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR.

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.