Essays on Nonlinearities and Structural Breaks in the Relationships between Macroeconomic Variables

The dissertation is set out in three chapters, focusing on the structural changes that led to jobless recoveries in following the past three recessions, the asymmetric effects of fiscal stimulus over the business cycle, and the asymmetric effects of fiscal cuts and stimulus respectively. In the first chapter, I examine the three leading theoretical explanations for the recent jobless recoveries using a correlated unobserved components model of aggregate data for output, sales, employment, and hours. The main finding is that employment now respond to demand shocks in a way that is consistent with just-in-time utilization of labor resources. The second and the third chapter focus on asymmetric responses to fiscal policy. In the second chapter, I investigate the effects of government spending on U.S. economic activity using a threshold version of a structural vector autoregressive model. The empirical findings support state-dependent effects of fiscal policy. In particular, the effects of a government spending shock on output are significantly larger and more persistent when the economy has a high degree of underutilized resources than when the economy is close to capacity. The third chapter examines whether there are sign and size asymmetries in the responses of output, output components, and employment to fiscal policy. When the economy is not constrained, a large fiscal stimulus is more effective at increasing employment and output, and cuts have larger effects than increases

A Likelihood Ratio Test of Stationarity Based on a Correlated Unobserved Components Model

We propose a likelihood ratio (LR) test of stationarity based on a widely-used correlated unobserved components model. We verify the asymptotic distribution and consistency of the LR test, while a bootstrap version of the test is at least first-order accurate. Given empirically-relevant processes estimated from macroeconomic data, Monte Carlo analysis reveals that the bootstrap version of the LR test has better small-sample size control and higher power than commonly used bootstrap Lagrange multiplier (LM) tests, even when the correct parametric structure is specified for the LM test. A key feature of our proposed LR test is its allowance for correlation between permanent and transitory movements in the time series under consideration, which increases the power of the test given the apparent presence of non-zero correlations for many macroeconomic variables. Based on the bootstrap LR test, and in some cases contrary to the bootstrap LM tests, we can reject trend stationarity for U.S. real GDP, the unemployment rate, consumer prices, and payroll employment in favor of nonstationary processes with volatile stochastic trends.Stationarity Test, Likelihood Ratio, Unobserved Components, Parametric Bootstrap, Monte Carlo Simulation, Small-Sample Inference

Molecular Monitoring in Acute Myeloid Leukemia Patients Undergoing Matched Unrelated Donor: Hematopoietic Stem Cell Transplantation

Minimal residual disease (MRD) in acute myeloid leukemia (AML) is a complex, multi-modality assessment and much as its clinical implications at different points are extensively studied, it remains even now a challenging area. It is the disease biology that governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. In AML patients undergoing allogenic hematopoietic stem cell transplantation (alloHSCT), relapse in considered as leading cause for treatment failure. In post-transplant setting, regular MRD status assessment enables to identify patients at risk of impending relapse when early therapeutic intervention may be beneficent. We analyzed data of AML patients who underwent matched unrelated donor (MUD) HSCT since the introduction of this procedure in the Republic of North Macedonia. Chimeric fusion transcripts were identified in three patients; two of them positive for RUNX-RUNX1T1 transcript and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was measured by quantitative polymerase chain or multiplex fluorescent-PCR every three months after the transplantation during the first two years after the transplant. MRD negativity was achieved in three patients by the sixth month of HSCT, who were pre-transplant MRD positive. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The forth patient died due to transplant-related complication. Our experience suggests, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies

Is Business Cycle Asymmetry Intrinsic in Industrialized Economies?

We consider a model-averaged forecast-based estimate of the output gap to measure economic slack in ten industrialized economies. Our measure takes changes in the long-run growth rate into account and, by addressing model uncertainty using equal weights on different forecast-based estimates, is robust to different assumptions about the underlying structure of the economy. For all ten countries in the sample, we find that the estimated output gap has much larger negative movements during recessions than positive movements in expansions, suggesting business cycle asymmetry is an intrinsic characteristic of industrialized economies. Furthermore, the estimated output gap is always strongly negatively correlated with future output growth and unemployment and positively correlated with capacity utilization. It also implies a convex Phillips Curve in many cases. The model-averaged output gap is reliable in real time in the sense of being subject to relatively small revisions

Cyclic voltammetry as a sensitive approach in investigation of doxorubicin

Introduction and objective Doxorubicin is an anthracycline drug. Its chemotherapeutic effect is due to two possible mechanisms, 1)disruption of topoisomerase-II-mediated DNA repair due to its intercalation into DNA helix and 2)generation of free radicals and their damage to cellular membranes, DNA, and proteins. This can be a result of its planar aromatic chromophore which intercalates between two base pairs of DNA [1]. Therefore, its pharmacological/toxicological characteristics are largely dependent on its oxidative properties, and the aim of this study is to summarize the methods and data based on its еlectrochemical behavior of doxorubicin, obtained by the means of cyclic voltammetry (CV) [2]. Methods Cyclic voltammetry is a versatile electrochemical method where the redox reactions occurring at the working electrode result in a flow of current. The potentiostat measures this current and plots it as a function of the applied potential. Each successful forwards and backwards potential sweep produces a a cyclic voltammogram characterized by anodic and cathodic peak currents, peak potentials, and the oxidation and reduction onset potentials. Results Our research revealed several studies that feature the electrochemical behavior of doxorubicin. CV in pH~7.4 has shown that doxorubicin undergoes a reversible two-electron reduction with value E1/2 = -665 mV(versus Ag/AgCl, saturated KCl). This process was defined as quasi reversible, at low scan rates. Further, the interaction of doxorubicin hydrochloride with calf thymus DNA was studied by measuring cathodic peak current, which gradually decreased as more DNA was added into the cell [3]. The interaction of doxorubicin with calf thymus DNA, was mostly assessed by electrochemical sensors using surface modified working electrodes [4,5,6]. Electrochemical sensor based on multi-walled carbon nanotubes modified platinum electrode (Pt/MWCNTs) [4], electrodeposition of silver nanoparticles and electro-polymerization of alginate layers on the surface of a glassy carbon electrode have been also used in this purpose [5]. CV of doxorubicine on a screen-printed electrodes modified with single-wall carbon nanotubes (SPE/CNT) have shown linear dependence of the intensity of electro reduction/oxidation on the square root of the scan rate which proved that the process is a controlled by diffusion. Moreover, thay imployed differential pulse voltammetry to validate a sensitive method for doxorubicine quantification. The drug binding processes were examined by DPV via the registration of a decrease in peak current intensity of guanine, adenine, and thymine of DNA in the presence of doxorubicin [6]. Conclusion Cyclic voltammetry can be used as an efffective tool for quantification of doxorubicine and its interactions with DNA or other metals. Reverible oxidation of doxorubicin to semiquinone and back, releases reactive oxygen species that cause DNA damage and lipid peroxidation. The effectivness of the therapeutic effect of doxorubicine depends on its interaction with DNA. These interactions were mostly assessed by using an electrochemical surface modified sensor, in the presence of DNA. These data lead to a conclusion that electrochemical platforms represent a sensitive approach for the investigation of DNA–drug interaction in electrode systems. Examining the electrochemical signals doxorubicin or DNA–doxorubicin complex before and after binding establishes the interaction and helps in mechanism elucidation

Sustainability of the Pension System in the Republic of Macedonia: Challenges and Solutions

The aim of the study is to create a forecasting model that will foresee the trend of the situation of the Pension, Insurance and Disability Fund of the Republic ofMacedonia. The methodology applied to evaluate the sustainability of pension system, and controlling the risk to pension funds, is forecast of all individual regressors through first order autoregressive model. This method will enable the assessment of the future uncertainty of the contributions and expenditures of pension insurance. The forecasted data show that in 2056, if no other reforms are undertaken, the increase in the percentage points of the number of employers is less than the increase in the number of pensioners for 3.9 percentage points. As per the natality and mortality, in the Republic of Macedonia natality will be only one third of its statistics in 2016, whereas mortality will double its value by 2056

Clinical Significance of Minimal Residual Disease at the End of Remission Induction Therapy in Childhood Acute Lymphoblastic Leukemia

BACKGROUND: Detection of minimal residual disease (MRD) in the early phase of therapy is the most powerful predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL). AIM: We aimed to determine the significance of MRD at the end of remission induction therapy in the prediction of treatment outcome in children with ALL. METHODS: Sixty-four consecutive patients aged 1-14 years with newly diagnosed ALL were enrolled in this study from January 2010 to October 2017. All patients were treated according to the ALL IC BFM 2002 protocol. MRD was detected at the end of remission induction therapy (day 33) by multiparameter 6-colour flow cytometry performed on bone marrow specimens with a sensitivity of 0.01%. RESULTS: Overall, 42.2% of patients had detectable MRD on day 33 of therapy. MRD measurements were not significantly related to presenting characteristics but were associated with a poorer blast clearance on day 8 and 15 of remission induction therapy. Patients with negative MRD status on day 33 had a 5-year event-free survival of 94.6% compared with 76.1% for those with positive MRD status (P = 0.044). CONCLUSION: MRD levels at the end of remission induction therapy measured by multiparameter flow cytometry have clinical significance in childhood ALL. High levels of MRD are strongly related to poor treatment outcome

Use of chronic lymphocytic leukemia-international prognostic index in patient risk stratification-single center experience

Background: Several prognostic factors have been identified to predict the outcome of patients with chronic lymphocytic leukemia (CLL). To predict the time to first treatment (TFT) we integrated the data of clinical and biological markers in CLL-International prognostic index (CLL-IPI). Aim of the study was the determination of the impact of CLL-IPI in prediction of TFS in CLL patents.Methods: The study was set up retrospectively and included 90 patients with CLL diagnosed and treated at the university clinic of hematology for a period of time from January 2012 to January 2020. We incorporated the data of Binet staging system, most adverse cytogenetic marker and mutational status of immunoglobulin heavy chain in CLL-IPI.Results: The statistical data of the 90 patients showed that the median TFS for low CLL-IPI (N=24), intermediate CLL-IPI (N=40), high risk CLL-IPI (N=17) and very high risk group (N=9) according to the CLL-IPI scoring system was 20.1, 17.6, 7.1 and 5.8 months, respectively. Multivariate analysis indicated that del 17p (p<0.008) was independent prognostic factors of TFS.Conclusions: CLL-IPI is a powerful risk stratification tool for CLL patients and this system has also provided treatment recommendations for different patient risk subgroups.