Panel Data Analysis Of The American Recovery And Reinvestment Act

The proposed study seeks to evaluate the merits of the American Recovery and Reinvestment Act of 2009 (commonly referred to as the “stimulus”) against its trifold objectives of: (a) creation of new jobs and protection of existing ones; (b) promotion of economic activity and sustainment of long-term growth; and (c) implementation of accountability and transparency in government spending. In a previous cross sectional analysis conducted by the authors, the stimulus provided by the government was found to have no effect on the housing prices. Therefore, the utility of the Act is questionable. In the current study, we look at one of the three modes in which the Act attempted to achieve its objectives and analyze it in depth. The analysis uses a 8-year panel data set across all 50 states in the United States. Results obtained from this analysis are expected to increase the efficacy of the implementable policy measures to ensure that the objectives and the results of the policy conform in similar future situations.Undergraduat

Discovery of a Cholinergic Circuit That Relieves Pain, despite Opioid Tolerance

Chronic pain pathologies plague society. While opioids effectively relieve pain, significant side effects, abuse liability, and development of analgesic tolerance outweigh their benefits. Furthermore, increasing levels of opioid prescription and repeated subsequent use has led to the current opioid epidemic, requiring substantive research efforts, as evidenced by the NIH’s Helping to End Addiction Long-term Initiative (HEAL) initiative. Whether other endogenous neuromodulators and their receptors can be harnessed to relieve pain with efficacy similar to opioids has not been thoroughly explored. The role of the neuromodulator Acetylcholine (ACh) in CNS function has been enigmatic. In this thesis, we explored the role of ACh in the ventrolateral periaqueductal gray (vlPAG), a key nucleus of the descending pain modulatory pathway. We found that nocifensive behaviors decreased ACh release in the vlPAG. Additionally, reversing this decrease in ACh by selectively activating cholinergic projections from Pedunculopontine Tegmental Nucleus (PPTg) to the vlPAG decreased the somatic and affective components of acute and chronic pain in opioid naïve and tolerant mice. We determined that the antinociceptive effects of this cholinergic circuit were mediated through ⍺7 nicotinic acetylcholine receptors (nAChR), which are co-expressed on μ-opioid receptor-expressing (Oprm1+) GABAergic vlPAG neurons. Parallel in vivo experiments revealed an unexpected physiological impact of ɑ7 nAChRs activation: these non-selective cation channels inhibited neuronal activity in a cell-autonomous manner multiple minutes after receptor activation. Using molecular biology and slice electrophysiology, we identified the intracellular signaling mechanism underlying this counter-intuitive decrease in activity: activation of ɑ7 nAChRs decreased neuronal excitability by phosphorylating voltage-gated potassium channels, a mechanism similar to the mechanism proposed for opioid receptors in the vlPAG. Finally, we explored the manifestation and progression of chronic pain state and opioid tolerance in the vlPAG in vivo. The value of obtaining insights in awake-behaving animals is perhaps of utmost importance in the descending pain modulatory pathways, given that the central dogma comes from work conducted in lightly anesthetized animals, which has been questioned. In this thesis, we use 2-photon imaging to track the progression of aberrant neuronal ensemble dynamics. This work leads to unexpected insights into the recruitment of non-pain-responsive neurons into the pain-encoding ensemble. We also observe that ⍺7 nAChRs agonists effectively relieve pain by inhibiting the Oprm1+ pain-sensitive neuronal ensembles in the vlPAG, even in opioid-tolerant animals. Finally, unlike opioids, ⍺7 nAChRs agonists did not show the development of tolerance, reward profile, or withdrawal symptoms. To obtain these insights, we have employed methods that allow for rigorous cross-verification at multiple levels. Cross-disciplinary approaches include mRNA measurements, cell-type specific anatomical tracing, ex-vivo electrophysiology to assay receptor function and neuronal excitability, and in-vivo 2-photon imaging to track the cellular basis for the onset and progression of chronic pain and opioid tolerance. These assays are supplemented by cell-type and circuit-specific manipulations to assay the impact on sensory and affective-motivational aspects of pain behaviors. Together, these investigations identify a novel circuit that modulates pain signaling and non-opioid therapeutic targets for the management of chronic pain

Global longitudinal strain, ejection fraction, effort tolerance and normal echocardiography measurements in healthy Indians

Introduction: Normative comprehensive echocardiographic measurements data for healthy Indians are not available while data for American and European population is available from American Society of echocardiography and European Society of Cardiology/European Association of Cardio-Vascular Imaging and their publications. Available studies of Indian subjects are small and report only limited measurements with focus on left ventricular (LV) volumes. Objective: We aim to provide comprehensive normative echocardiographic data for healthy Indians from a large sample size. Methods: A retrospective cross-sectional single-center study of 707 healthy Indian adults age and sex segregated which presented detailed and comprehensive echocardiographic measurements including two-dimensional, M-mode, tissue Doppler imaging, speckle tracking echocardiography, chamber volumes, LV ejection fraction (LVEF), global longitudinal strain (GLS), segmental longitudinal strain and effort tolerance. Results: Our findings show healthy Indians, as compared to US and European population, to have higher relative wall thickness. LV volumes, LV mass, LVEF and effort tolerance that were within American Society of Echocardiography described ranges for chamber quantification. Higher GLS values were observed in Indian population compared to European and American population. Women had higher LVEF and GLS values as compared to men and both showed a gradual decline with aging. Conclusion: We present normal reference values for echocardiographic measurements in healthy Indian population, which could be used for future reference and comparison work. Keywords: Echocardiography normative data, Global longitudinal strain, LV ejection fraction, Effort tolerance, Indian adult

On foreclosure rates and the house price index: A cross-sectional analysis

This paper attempts to firmly establish the dependence of house price index on foreclosure rates, a prerequisite to substantiating “let-sink” foreclosure policy. In our paper, we first examine a simple linear regression model to show that there are omitted variables in the model, and therefore, more variables other than just foreclosure rates have to be considered. We then continue with the multiple linear regression model by looking at the influence of foreclosure rates, education, property tax, income tax, stimulus, and legal system upon house price index. By using this model, we show that most variables do not have statistical significance, individually or jointly, except for foreclosure rates and legal system. Finally, we reject the null hypothesis and conclude that house price index is significantly dependent upon foreclosure rates and the state legal foreclosure system

A cholinergic circuit that relieves pain despite opioid tolerance

Chronic pain is a tremendous burden for afflicted individuals and society. Although opioids effectively relieve pain, significant adverse outcomes limit their utility and efficacy. To investigate alternate pain control mechanisms, we explored cholinergic signaling in the ventrolateral periaqueductal gray (vlPAG), a critical nexus for descending pain modulation. Biosensor assays revealed that pain states decreased acetylcholine release in vlPAG. Activation of cholinergic projections from the pedunculopontine tegmentum to vlPAG relieved pain, even in opioid-tolerant conditions, through ⍺7 nicotinic acetylcholine receptors (nAChRs). Activating ⍺7 nAChRs with agonists or stimulating endogenous acetylcholine inhibited vlPAG neuronal activity through Ca2+ and peroxisome proliferator-activated receptor α (PPAR⍺)-dependent signaling. In vivo 2-photon imaging revealed that chronic pain induces aberrant excitability of vlPAG neuronal ensembles and that ⍺7 nAChR-mediated inhibition of these cells relieves pain, even after opioid tolerance. Finally, pain relief through these cholinergic mechanisms was not associated with tolerance, reward, or withdrawal symptoms, highlighting its potential clinical relevance