Site-Specific and Country-of-Origin Labeling for Pharmaceutical Manufacturing

There is increasing concern about the quality of pharmaceuticals, especially generics made in Asia. Popular books and news reports have the public questioning the quality of pharmaceuticals. Recalls and import bans shake confidence in medications, particularly for active pharmaceutical ingredients and finished dosage forms made outside the United States. The Food and Drug Administration uses geography to allocate resources for manufacturing surveillance. Site of manufacturing labeling, including the country, could be linked to the facility’s quality score to assess the risk of poor quality. Clinicians should advocate for legal and regulatory changes to increase the transparency of pharmaceutical manufacturing of products.

Communicating The Amil Zakat National Agency (BAZNAS) and Its Authority Based on the Zakat Management Act (23/2011) in Indonesi

This research aimed to see how BAZNAS communicates its authority based on Law 23/2011 to its stakeholders. Zakat management in Indonesia is being regulated by the Law Number 23 of 2011 which replaced Law Number 38 of 1999. The change of regulation was expected to push Zakat collection higher as its great potential, but until 2019 there was no significant change in the amount of Zakat collection. We see the problem in the authority changes that have not working optimally. Thus, this research can help BAZNAS to map out the problems related to the implementation of Law 23/2011. The research used a qualitative approach by conducting in-depth interviews, library and documentation studies. Eleven expert informants were chosen for their connection and understanding of BAZNAS. The results showed that the BAZNAS authority was accepted by all stakeholders even though it did not take place as the prerequisite for the acceptance of Barnard's authority. The changes in authority had been understood by the leaders but only halfway understood by the employees. The changes in the authority were following the vision and mission of BAZNAS. However, they were still not in line with the expectations of many parties. Finally, the changes in the BAZNAS authority were still not fully implemented by BAZNAS stakeholders. The regulatory changes could not be fully implemented yet due to differences in the interpretation of legal authority between each level of BAZNAS.

Elite Triathlete Profiles in Draft-Legal Triathlons as a Basis for Talent Identification

Draft-legal triathlons are the main short-distance races worldwide and are those on which talent-identification programs are usually focused. Performance in these races depends on multiple factors; however, many investigations do not focus on elite triathletes. Therefore, the aim of this narrative review was to carry out a systematic literature search to define the elite female and male triathlete profiles and their competition demands in draft-legal triathlons. This will allow us to summarize the main determinant factors of high-level triathletes as a basis for talent detection. A comprehensive review of Web of Science and Scopus was performed using the search strategy: Triathl* and (performance or competition or profile) and (elite or professional or “high performance” or “high level” or talent). A total of 1325 research documents were obtained, and after screening following the criteria, only 83 articles were selected. After data synthesis, elite triathlete aspects such as age, physiological, anthropometric, and psychosocial profile or competition demands were studied in the scientific literature. Thus, it is essential that when implementing talent identification programs, these factors must be considered. However, constant updating is needed due the continuous regulatory changes and the need of triathletes to adapt to these new competition demands.

Caring but sharing unintentionally: Lobbying for innovations and the leakage of knowledge

When firms engage in lobbying, their intended outcome is a regulatory change that benefits them. However, prior literature suggests that there may also be an unintended outcome of lobbying—the leakage of knowledge to competitors. In this paper, I explore when the intended and the unintended outcomes are more likely by theorizing about the relationship between lobbying and innovation. I predict that innovations that are novel are more likely to benefit from the intended regulatory changes. However, innovations that use knowledge uniquely possessed by a few firms are more likely to be compromised by the leakage of knowledge that happens during lobbying. I use new data from 1999-2013 on public U.S. firms that engaged in lobbying to federal agencies, the regulatory changes made by federal agencies, and the 16,000 patents applied for by those firms. I employ unsupervised machine learning (Doc2Vec) to measure knowledge leakage and an instrumental variable 2SLS mediation analyses to test the theory. The results suggest that the intended regulatory changes that follow lobbying can benefit innovations by facilitating wider adoption. However, unique technological knowledge that only a few firms possess may be expropriated by competitors during the process of lobbying. Overall, this paper demonstrates that fundamental aspects of innovation— such as institutional change, knowledge transfer, and technology adoption—are closely related to lobbying, a form of nonmarket activity.

Sex-specific evolution of a Drosophila sensory system via interacting cis- and trans-regulatory changes

The evolution of gene expression via cis-regulatory changes is well established as a major driver of phenotypic evolution. However, relatively little is known about the influence of enhancer architecture and intergenic interactions on regulatory evolution. We address this question by examining chemosensory system evolution in Drosophila. D. prolongata males show a massively increased number of chemosensory bristles compared to females and males of sibling species. This increase is driven by sex-specific transformation of ancestrally mechanosensory organs. Consistent with this phenotype, the Pox neuro transcription factor (Poxn), which specifies chemosensory bristle identity, shows expanded expression in D. prolongata males. Poxn expression is controlled by non-additive interactions among widely dispersed enhancers. Although some D. prolongata Poxn enhancers show increased activity, the additive component of this increase is slight, suggesting most changes in Poxn expression are due to epistatic interactions between Poxn enhancers and trans-regulatory factors. Indeed, the expansion of D. prolongata Poxn enhancer activity is only observed in cells that express doublesex (dsx), the gene that controls sexual differentiation in Drosophila and also shows increased expression in D. prolongata males due to cis-regulatory changes. Although expanded dsx expression may contribute to increased activity of D. prolongata Poxn enhancers, this interaction is not sufficient to explain the full expansion of Poxn expression, suggesting that cis-trans interactions between Poxn, dsx, and additional unknown genes are necessary to produce the derived D. prolongata phenotype. Overall, our results demonstrate the importance of epistatic gene interactions for evolution, particularly when pivotal genes have complex regulatory architecture.

Evolution of a New Testis-Specific Functional Promoter Within the Highly Conserved Map2k7 Gene of the Mouse

Map2k7 (synonym Mkk7) is a conserved regulatory kinase gene and a central component of the JNK signaling cascade with key functions during cellular differentiation. It shows complex transcription patterns, and different transcript isoforms are known in the mouse (Mus musculus). We have previously identified a newly evolved testis-specific transcript for the Map2k7 gene in the subspecies M. m. domesticus. Here, we identify the new promoter that drives this transcript and find that it codes for an open reading frame (ORF) of 50 amino acids. The new promoter was gained in the stem lineage of closely related mouse species but was secondarily lost in the subspecies M. m. musculus and M. m. castaneus. A single mutation can be correlated with its transcriptional activity in M. m. domesticus, and cell culture assays demonstrate the capability of this mutation to drive expression. A mouse knockout line in which the promoter region of the new transcript is deleted reveals a functional contribution of the newly evolved promoter to sperm motility and the spermatid transcriptome. Our data show that a new functional transcript (and possibly protein) can evolve within an otherwise highly conserved gene, supporting the notion of regulatory changes contributing to the emergence of evolutionary novelties.

Cities in Developing Countries (CiDC)

This chapter addresses cities in developing countries that suffer from lack of economic resources and limited capabilities of the society. The chapter provides a definition of an economically productive city and the supports it needs from the national central government. Governance issues related to the local government are described, such as low citizen engagement, necessary legislative/regulatory changes, managing increasing citizen expectations, and community planning issues. It also touches on the issues of transparency and open government, operational inefficiencies, and ever-increasing urbanization movement. An important part of this chapter is touching on preparing for partial transformation and identifying opportunities and threats. It also provides guidelines for a general roadmap of actions that are based on planning a smart city, partnerships, and policies. Finally, transformation guidelines are discussed such as challenges for smart city transformation, alignment with national e-governance, capacity building, and change management.

Determinants of Political Stability to Support Foreign Investment in Indonesia

What investors often consider before deciding to invest in various countries is the political situation. The risks faced by investors in the event of political instability are regulatory changes, legal disputes, forced takeovers of companies, disruption to regional stability, policies against acts of terrorism, and changes in state ideology. The purpose of this study is to find a determinant of political stability in Indonesia that will be useful for investors and multinational companies, and the government in maintaining political stability. Systematic secondary data sampling from January 2015 to December 2019 was used for explanatory study purposes and to build a model. This study concludes that the rule of law, control of corruption, and oil prices have a significant effect on political stability in Indonesia, while the inflation rate does not have a significant effect on political stability in Indonesia. The novelty of this research is the formation of a political stability model for Indonesia and why an increase in control of corruption actually has a negative effect on political stability in Indonesia.

Evolution of stickleback spines through independent cis-regulatory changes at HOXDB

Understanding the genetic mechanisms leading to new traits is a fundamental goal of evolutionary biology. We show that HOXDB regulatory changes have been used repeatedly in different stickleback fish species to alter the length and number of bony dorsal spines. In Gasterosteus aculeatus, a variant HOXDB allele is genetically linked to shortening an existing spine and adding a spine. In Apeltes quadracus, a variant allele is associated with lengthening an existing spine and adding a spine. The alleles alter the same conserved non-coding HOXDB enhancer by diverse molecular mechanisms, including SNPs, deletions, and transposable element insertions. The independent cis-acting regulatory changes are linked to anterior expansion or contraction of HOXDB expression. Our findings support the long-standing hypothesis that natural Hox gene variation underlies key morphological patterning changes in wild populations and illustrate how different mutational mechanisms affecting the same region may produce opposite gene expression changes with similar phenotypic outcomes.