Systems biology in drug discovery Butcher, Eugene C; Berg, Ellen L; Kunkel, Eric J
Nature biotechnology,
10/2004, Letnik:
22, Številka:
10
Journal Article
Recenzirano
The hope of the rapid translation of 'genes to drugs' has foundered on the reality that disease biology is complex, and that drug development must be driven by insights into biological responses. ...Systems biology aims to describe and to understand the operation of complex biological systems and ultimately to develop predictive models of human disease. Although meaningful molecular level models of human cell and tissue function are a distant goal, systems biology efforts are already influencing drug discovery. Large-scale gene, protein and metabolite measurements ('omics') dramatically accelerate hypothesis generation and testing in disease models. Computer simulations integrating knowledge of organ and system-level responses help prioritize targets and design clinical trials. Automation of complex primary human cell-based assay systems designed to capture emergent properties can now integrate a broad range of disease-relevant human biology into the drug discovery process, informing target and compound validation, lead optimization, and clinical indication selection. These systems biology approaches promise to improve decision making in pharmaceutical development.
Recent evidence suggests that legal marijuana markets in several U.S. states have decreased violence in Mexican-U.S. border regions. As legal markets for production and distribution displace drug ...cartel distribution, the violence associated with cartel trafficking and distribution decreases. Prior analysis has not considered an important emerging innovation for drug distribution: online anonymous marketplaces. The increasing volume of drug trade that has occurred on this “Dark Web” could result in reduced drug cartel violence as production and distribution use this substitute network and turn away from the cartel distribution networks. This paper investigates the relationship between border violence and the volume of drug trade that occurs on the Dark Web using a difference in differences model. We examine differences in crime rates at the U.S.-Mexico border and away from the border during the emergence of the Dark Web. Data on Dark Web transactions, users, and markets allows us to measure changes in Dark Web activity and the subsequent impact on crime. We find evidence that the rise in Dark Web marketplaces results in crime reductions at the border of the U.S., relative to non-border counties.
Since the cloning of the histamine H(3) receptor cDNA in 1999 by Lovenberg and co-workers, this histamine receptor has gained the interest of many pharmaceutical companies as a potential drug target ...for the treatment of various important disorders, including obesity, attention-deficit hyperactivity disorder, Alzheimer's disease, schizophrenia, as well as for myocardial ischaemia, migraine and inflammatory diseases. Here, we discuss relevant information on this target protein and describe the development of various H(3) receptor agonists and antagonists, and their effects in preclinical animal models.
Biomarkers enable the characterization of patient populations and quantitation of the extent to which new drugs reach intended targets, alter proposed pathophysiological mechanisms and achieve ...clinical outcomes. In genomics, the biomarker challenge is to identify unique molecular signatures in complex biological mixtures that can be unambiguously correlated to biological events in order to validate novel drug targets and predict drug response. Biomarkers can stratify patient populations or quantify drug benefit in primary prevention or disease-modification studies in poorly served areas such as neurodegeneration and cancer. Clinically useful biomarkers are required to inform regulatory and therapeutic decision making regarding candidate drugs and their indications in order to help bring new medicines to the right patients faster than they are today.
Using US panel data on young workers, we demonstrate that those who receive performance pay are more likely to consume alcohol and illicit drugs. Recognizing that this likely reflects worker sorting, ...we first control for risk, ability, and personality proxies. We further mitigate sorting concerns by introducing worker fixed effects, worker-employer match fixed effects, and worker-employer-occupation match fixed effects. Finally, we present fixed effect IV estimates. All of these estimates continue to indicate a greater likelihood of substance use when a worker receives performance pay. The results support conjectures that stress and effort increase with performance pay and that alcohol and drug use is a coping mechanism for workers.
The poetry of Anelisa Thengimfene, through scholarly critique, certifies that applicatory subjects may be enacted in isiXhosa modern literature. Such applicatory subjects breathe pertinence to social ...issues that predominantly affect the South African youth and other organs of social anatomy. Using Anelisa Thengimfene's two selected isiXhosa poems (Imfundo andIziyobisi) , issues concerning education and drug abuse are critiqued in terms of content or subject matter in order to unmask their interfacing meanings. Textual analysis alongside qualitative research methodology is appointed to operate in a synergetic relationship. The principal objective of this article is to exhibit that education and drug addiction are social problems that continue to sabotage the lives of many young men and women in South Africa and elsewhere. The findings and discussions underscore that isiXhosa modern literature should be employed for the fact that it contests contemporary issues that are valuable and worth theoretical and practical debates. As a direct consequence of that, the closing remarks recommend a maintained scrutinisation of isiXhosa modern poetry. The contribution of this intellectual discourse can be pinned on the fact that Anelisa Thengimfene is an emerging isiXhosa literary writer, and therefore, new insights can be enacted from her literary art.
Recreational cannabis and opioid distribution Raman, Shyam; Maclean, Johanna Catherine; Bradford, W. David ...
Health economics,
April 2023, Letnik:
32, Številka:
4
Journal Article
Recenzirano
Twenty‐one U.S. states have passed recreational cannabis laws as of November 2022. Cannabis may be a substitute for prescription opioids in the treatment of chronic pain. Previous studies have ...assessed recreational cannabis laws' effects on opioid prescriptions financed by specific private or public payers or dispensed to a unique endpoint. Our study adds to the literature in three important ways: by (1) examining these laws' impacts on prescription opioid dispensing across all payers and endpoints, (2) adjusting for important opioid‐related policies such as opioid prescribing limits, and (3) modeling opioids separately by type. We implement two‐way fixed‐effects regressions and leverage variation from eleven U.S. states that adopted a recreational cannabis law (RCL) between 2010 and 2019. We find that RCLs lead to a reduction in codeine dispensed at retail pharmacies. Among prescription opioids, codeine is particularly likely to be used non‐medically. Thus, the finding that RCLs appear to reduce codeine dispensing is potentially promising from a public health perspective.
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