A Note on "Crowding Out" in the United States

This study examines the existence of crowding out in the United States by determining to what degree the proportion of actual GNP that was devoted to investment was affected by the proportion of GNP devoted to federal government spending. The empirical results in the regression estimation tentatively indicate that private investment in new capital is in fact crowded out by federal government outlays. Nevertheless, the evidence in this regression indicates also that although crowding out does occur, it is incomplete

A Note on "Crowding Out" in the United States

This study examines the existence of crowding out in the United States by determining to what degree the proportion of actual GNP that was devoted to investment was affected by the proportion of GNP devoted to federal government spending. The empirical results in the regression estimation tentatively indicate that private investment in new capital is in fact crowded out by federal government outlays. Nevertheless, the evidence in this regression indicates also that although crowding out does occur, it is incomplete

The Drug Overdose Epidemic Seen through Different Lenses

The age-adjusted death rate from drug overdoses in the United States per 100,000 individuals rose from 6.8 in 2010 to 17.1 in 2018. The most common explanation offered is the deaths of despair hypothesis. We identify additional factors that have contributed to the rise in drug overdose deaths in cities and counties. Methods: We utilize a period fixed effects model with a multi-variate panel data set for 94 independent cities and counties in Virginia for the period 2008 through 2017. Results: The drug overdose mortality rate is: (a) an increasing function (prob

Drug-Overdose Death Rates: The Economic Misery Explanation and Its Alternatives

‘Deaths of despair’ is the most commonly cited explanation for the 151% increase in drug-overdose deaths that occurred in the USA between 2010 and 2018. We use panel data describing 84 Virginia cities and counties to assess the validity of the deaths of despair hypothesis and alternate explanations that focus on disability rates, travel time to work, urban vs. rural location, educational attainment, racial and ethnic characteristics, the influence of other health conditions such as obesity, and supply-side factors that include pill availability and pharmacy market shares. We find deaths of despair to be only a partial explanation for the upsurge in drug-overdose deaths and conclude that a much broader view of the causes of drug-overdose deaths is merited

Towards the Application of Atorvastatin to Intensify Proapoptotic Potential of Conventional Antileukemic Agents In Vitro

It has been previously revealed that statins used at high concentrations display antileukemic potential towards chronic lymphocytic leukemia (CLL) cells. However, their usage alone in clinical practice may be limited due to possible side effects of high doses of these drugs. On the other hand, combined treatment of leukemia with statins and the conventional chemotherapeutics is questionable because of unknown influence of the first on the standard treatment results. This study has revealed that in vitro atorvastatin increases the proapoptotic potential of cladribine and mafosfamide in CLL cells isolated from peripheral blood of patients. Moreover, a preincubation with the above statin sensitizes leukemic cells to CM-induced apoptosis even at small concentrations of the drug. The usage of atorvastatin together with or followed by the conventional chemotherapy should be considered as therapeutic option for the treatment for this leukemia. Interestingly, CM-resistant patients might have the biggest benefits from atorvastatin administration.Grant no. 1407 from the University of Łódź

POTENTIAL GENETIC AGENT BFL1 FOR TARGETED THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA

Background: Many prognostic factors have been identified in chronic lymphocytic leukemia (CLL) but new ones are still desired. The biological characterization of CLL is now being translated into novel treatment strategies. One new prognostic factor, and therapeutic target, may be BFL1. It is both a serum and a molecular marker that contributes to the progression of CLL and its resistance to chemotherapy. The aim of this study was to evaluate the prognostic value of BFL1 and to assess its correlation with other known prognostic markers in CLL for the cladribine and cyclophosphamide regimen (CC). Methods: qPCR TaqMan® Low Density Array was used for gene expression measurements. Assessment of CD38, ZAP70 and BFL-1 proteins expression was done by means of flow cytometry. Serum TK activity was measured by immunoassay. Results: Protein BFL1 expression was found to be significantly higher in CLL patients than healthy volunteers (p=0.001). Moreover its level was significantly higher in patients with no response (NR) to CC therapy (p=0.009). The expression of BFL1 was considerably down regulated during CC treatment and BFL1 mRNA levels were inversely correlated with apoptotic response. In addition, protein BFL1 expression was found to be similar to thymidine kinase (TK) concentration regarding treatment response. As far as other markers are concerned, a positive correlation was identified between BFL1 and TK (r=0.52, p=0.01). Conclusions: Our findings suggest that BFL1 contributes to chemoresistance and may be a co-existing prognostic factor in CLL in the future

The role of neuronal apoptosis inhibitory protein (NAIP) in acute myeloid leukemia patients

Acute myeloid leukemia (AML) is a heterogeneous, highly malignant neoplasm. Apoptosis is a complex process executed by caspases and suppressed by the inhibitor of apoptosis (IAP) family. Neuronal apoptosis inhibitory protein (NAIP), IAP’s member, may play an exceptional role in the mechanisms of tumors’ resistance to chemotherapy. The aims of the study were to assess the expression of NAIP in leukemic blasts of AML patients using flow cytometry and to evaluate its influence on disease outcome. NAIP expression was found in 106 out of 108 patients. A higher complete response rate was associated with a low expression of NAIP, age < 60 yo, and white blood cell count < 20 G/L ( = 0.009, = 0.033, and = 0.076, respectively) in univariate analyses and a low NAIP expression and age < 60 yo ( = 0.025 and = 0.013, respectively) in multivariate analyses. Longer overall survival (OS) in the univariate analysis was influenced by a low NAIP expression, age < 60 yo, and intensive chemotherapy ( = 0.033, < 0.001, and < 0.001, respectively). In the intensively treated group, better OS was observed in patients with age < 60 yo, AML, and a low NAIP expression ( = 0.03, = 0.024, and = 0.07, respectively). In multivariate analysis, longer OS was associated with age < 60 yo ( = 0.009) and AML ( = 0.007). In conclusion, we suggest that NAIP might play an adverse role in response to chemotherapy