Historical Success Research Articles

Unethical governance: capacity legislation and the exclusion of people diagnosed with dementias from research

This paper considers the potential for the Mental Capacity Act (MCA) of England and Wales to incentivise the exclusion of people with dementia from research. The MCA is intended to standardise and safeguard the inclusion of people with cognitive impairments in research. This entails various procedural requirements, which in pressurised research contexts can lead researchers to exclude people with dementia as a means of simplifying bureaucratic constraints. I consider the risks of an ‘unethical ethics’, wherein procedural ethics indirectly causes the exclusion of people with dementia from research, undermining historic successes toward increased inclusivity. I suggest several solutions, including enhanced sensitivity to impairments and shifting the burden of proof from justifying inclusion to justifying exclusion. The paper responds to the ‘ethics creep’ tradition in procedural ethics, and critical appraisals of capacity legislation in dementia research. This approach recognises that institutional research ethics is itself a major ethical concern and can unwittingly beget unethical practices. Dementia researchers must be alert to such unethical ethics.

The rationality of history and the history of rationality: Menachem Fisch on the analytic idealist predicament

AbstractTwo essential Kantian insights are the significance for rationality of the capacity for criticism and the limits of cognition, discovered when criticism is pursued methodically, that are due to the perspectival character of the human standpoint. After a period of disparagement, these Kantian insights have been sympathetically construed and are now discussed within contemporary analytic philosophy. However, if Kant’s assumption of a single, immutable, human framework is jettisoned, then the rationality of historical succession is called into question. Moreover, if the revolutionary character of framework transitions is acknowledged, then reason is historicized and even its character as reason is threatened. I argue that Menachem Fisch’s approach to criticism and rationality offers an escape from this post-Kantian predicament that acknowledges revolutionary framework transitions and that draws upon the dialogical traditions of Jewish thought, and I also argue that Fisch’s approach should be seen as thematizing, to use the terms of Kant’s aesthetics and of Fichte’s account of natural right, the reflecting rather than determining status of critical judgement, which involves second-personal address.

Mass administration of medicines in changing contexts: Acceptability, adaptability and community directed approaches in Kaduna and Ogun States, Nigeria.

Nigeria has the highest burden of NTDs in sub-Saharan Africa. Commitments to reach the control and elimination of many Neglected Tropical Diseases (NTDs), particularly those amenable to preventive chemotherapy (onchocerciasis, schistosomiasis, soil transmitted helminths, lymphatic filariasis and trachoma) by 2020 are detailed in the London declaration. Strategies to reach targets build on existing approaches, one of which is the use of community directed intervention (CDI) methods to deliver the mass administration of medicines (MAM). However, treatment using this approach has been inconsistent and there are questions about the acceptability and adaptability of these interventions during periods of programmatic, social, and political change. This paper explores the current strengths and weaknesses of CDI approaches in MAM delivery. We consider the acceptability and adaptability of existing MAM approaches to ensure equity in access to essential treatments. Using qualitative methods, we explore implementer perspectives of MAM delivery. We purposively selected programme implementers to ensure good programmatic knowledge and representation from the different levels of health governance in Nigeria. Data collection took place across two States (Kaduna and Ogun). Our results indicate that CDI approaches have underpinned many historic successes in NTD programme acceptance in Nigeria, specifically in Kaduna and Ogun State. However, our results also show that in some contexts, factors that underpin the success of CDI have become disrupted presenting new challenges for programme implementers. Capturing the tacit knowledge of health implementers at varying levels of the health system, we present the current and changing context of MAM delivery in Kaduna and Ogun States and consolidate a platform of evidence to guide future programme delivery and research studies. We situate our findings within the broader NTD literature, specifically, in identifying how our findings align to existing reviews focused on factors that shape individual acceptance of MAM.

In vitro Studies of Transendothelial Migration for Biological and Drug Discovery.

Inflammatory diseases and cancer metastases lack concrete pharmaceuticals for their effective treatment despite great strides in advancing our understanding of disease progression. One feature of these disease pathogeneses that remains to be fully explored, both biologically and pharmaceutically, is the passage of cancer and immune cells from the blood to the underlying tissue in the process of extravasation. Regardless of migratory cell type, all steps in extravasation involve molecular interactions that serve as a rich landscape of targets for pharmaceutical inhibition or promotion. Transendothelial migration (TEM), or the migration of the cell through the vascular endothelium, is a particularly promising area of interest as it constitutes the final and most involved step in the extravasation cascade. While in vivo models of cancer metastasis and inflammatory diseases have contributed to our current understanding of TEM, the knowledge surrounding this phenomenon would be significantly lacking without the use of in vitro platforms. In addition to the ease of use, low cost, and high controllability, in vitro platforms permit the use of human cell lines to represent certain features of disease pathology better, as seen in the clinic. These benefits over traditional pre-clinical models for efficacy and toxicity testing are especially important in the modern pursuit of novel drug candidates. Here, we review the cellular and molecular events involved in leukocyte and cancer cell extravasation, with a keen focus on TEM, as discovered by seminal and progressive in vitro platforms. In vitro studies of TEM, specifically, showcase the great experimental progress at the lab bench and highlight the historical success of in vitro platforms for biological discovery. This success shows the potential for applying these platforms for pharmaceutical compound screening. In addition to immune and cancer cell TEM, we discuss the promise of hepatocyte transplantation, a process in which systemically delivered hepatocytes must transmigrate across the liver sinusoidal endothelium to successfully engraft and restore liver function. Lastly, we concisely summarize the evolving field of porous membranes for the study of TEM.

Features of the socio-spatial organization of creative spaces of a modern city

Urban public spaces in the context of the sociology of architecture are considered, the definition of the urban creative space is given, the creative spaces’ role in the transformation processes of the formation of a modern urban environment is analyzed, the specifics of their organization forms and methods are considered in the article. It is proposed to use the existing public spaces adjoined to the houses of culture that often have their own unique history, identity and “memory of the place” as the platforms for the development of the city’s creative potential. The organization principles and methods of creative spaces in the context of Volgograd regional features based on the scenario approach that provides the development of the types: “scenography”, “activity”, “information”, “arrangement scenarios” are formulated. The conclusion about the need to preserve the specific city spaces containing outstanding historical elements and about the creative spaces’ formation on the basis of the historical succession principle built on a combination of historical objects and new environmental components is made.

О конституционно-правовых основах государственной политики в КНР

Purpose. Scientific justification of the idea on the acknowledgment of the role of priority basic constitutional principles as grounds for the constitutional law regulation of the state policy in the PRC. Methodology: dialectics, hermeneutics, synergetics, philosophical conceptology. Conclusions. Holding a discussion on the approaches of the modern comparative linguistics to the identification of the development principles of the Chinese legal system, the author suggests referring the Chinese legal system to the socialist one with national peculiarities, historical succession, Chinese traditions occupying an important place in the development of the socialist principle of democratic centralism of the Communist Party of China. The author notes that the key constitutional principles of organization of government in the PRC are established and developed using the elements of two legal families (far eastern, socialist) and taking into account the Chinese specifics of the ideological origination and development of the Communist Party of China based on the ideas of K. Marx, V. I. Lenin, Chinese leaders and other supporters of the democratic centralism principle. Based on the provisions of the first chapter of the Constitution of the PRC, the author singles out 32 categories of the key principles of the constitutional law formation of the Chinese state directly or indirectly forming the powers of government authorities, state policy fundamentals. Scientific and practical significance. The conclusions of the article are aimed at systematization of the key constitutional principles of organization of government in the PRC classified into: basic, economic, social, law enforcement, administrative-territorial and additional ones. The priority basic principles singled out by the author are designed to form the grounds for the constitutional law regulation of the state policy.

Systems engineering knowledge and skills for water and environmental problems

ABSTRACT Systems engineering is a discipline for organising problems and finding better solutions. The approach is ancient and practical in its origins, and has become more formal in the last century. Systems engineering usually involves assembling solutions that consist of diverse components to work effectively together, drawing from mechanics, science, and social science to better achieve explicit objectives. Because few problems can be solved by one person, many systems we engineer require the cooperation and involvement of thousands or millions of people, making social and political aspects central. This paper summarises some thoughts on formal and professional education for systems engineering and its application, including some historical successes and challenges for water and environmental problems. Perhaps the most single important aspect of applied system engineering is to organise the problem in a way that helps it to be more productively discussed and better solved.

Power in Networks: The Medici*

We use the Public Good (Power) Index and the Public Value to rank the marriages of business relations of 16 elite families in 15th century Florence – with a focus on the networks of the Medici and the taking of power by Cosimo de’ Medici. Theoretical analysis supports the outstanding position of the Medici family and explains much of its historical success. The paper offers material for the more general discussion of network rigidity versus social embeddedness, which concludes the paper.

Evolution of the European regional large mammals assemblages in the end of the Middle Pleistocene – The first half of the Late Pleistocene (MIS 6–MIS 4)

The Middle Pleistocene – Late Pleistocene transition of European large mammal's fauna (Proboscidea, Artiodactyla, Perissodactyla, Carnivora, Hystrix and Castor) assemblages has been studied in 18 European regional faunal assemblages. This study is based on the data yielded from 423 palaeontological sites (758 localities) dated within interval of MIS 6–MIS 4. All the data was aggregated by 9 time intervals (time scale). For ten bioregions, we have been able to obtain descriptive models of evolution of their faunal assemblages. It allowed detecting common rules of changes in large mammals' fauna composition in Europe on the whole as well as changes in the distribution of individual species and their groups within the regions. We have studied the changes in biodiversity parameters (Shannon index, index of self-organization) and Mourelle–Ezcurra species turnover index within MIS 6–MIS 4 time interval. The evolution of European fauna was compared for MIS 6–MIS 5 transition and MIS 2–MIS 1 transition as well as influence of change in global temperature on these transitions was described. In addition, we have showed the correlation between modern species richness with the species richness in MIS 6, MIS 5 and MIS 4 and proposed the hypothesis of historical succession of European bioregions.

Site selection methodology for emergency centers in Silk Road based on compatibility with Asian Highway network using the AHP and ArcGIS (case study: I. R. Iran)

Road transportation is a necessary part of the economic, cultural, martial, social, and tourism development of nations throughout history. For several centuries, Silk Road (SR) could provide a secure way of connecting Asian and European nations. Despite historical successes, the old SR has been inactive for several centuries. China has recently decided to revive the old road through the New SR Initiative. In this paper, the existing Asian highway (AH) network which passes through Iran and reaches Turkey is considered to revive SR. Most of the suggested routes of SR passing through Iran also pass through the AH network. One of the critical considerations for such a project is the issue of accident-wise road safety. According to the descriptive and spatial data analyses, and by leveraging ArcGIS, tentative routes in Iran were analyzed. The mentioned routes contain parts of the SR and parts of the existing AH network. Therefore, the goal of the analyses was to propose the best locations for the construction of the medical emergency centers, which can elevate the road's safety measures. To identify higher risk locations, four different criteria that affect safety were considered. These criteria include the distance from the city centers, the number of the available emergency stations, the number of rest, service, and lodging stations, and finally, the road accident frequency. To identify each factor's significance, a questionnaire was developed and filled by the road and transportation experts. This analysis was performed using the analytic hierarchical process in the ArcGIS platform. The risk assessment showed that the road between Garmsar and Tehran has the highest car accident risk among all other routes. Results can be used for further remedial actions to elevate safety along this route.

Exploratory Analysis of the Factors Associated With Success Rates of Confirmatory Randomized Controlled Trials in Cancer Drug Development.

This study examined the outcomes of recent confirmatory randomized controlled trials (RCTs) in phase III that were initiated between 2005 and 2017 for oncologic drugs in the United States and identified several factors that were associated with the success of RCTs. Our regression analysis showed that studies with progression‐free survival or response rate as primary end point were more likely to succeed than studies with overall survival (odds ratio (OR) = 2.94 and 6.23, respectively). The status of development was also linked with success rates. Studies for non‐lead indication tended to have lower success rates than studies for lead indication (OR = 0.68). Studies for first‐line therapy were observed to have low success rates compared with studies for post second‐line therapies (OR = 0.37). Studies for which strong prior evidence was not listed in their publication tended to be more successful than studies that followed rigorous RCTs or single arm studies for the indication. These results suggest that historical success rates may reflect not only the important features of trials, which can be observed directly from study design and results, but also the background status of trials in clinical development pathways.

Why Did Memetics Fail? Comparative Case Study

Although the theory of memetics appeared highly promising at the beginning, it is no longer considered a scientific theory among contemporary evolutionary scholars. This study aims to compare the genealogy of memetics with the historically more successful gene-culture coevolution theory. This comparison is made in order to determine the constraints that emerged during the internal development of the memetics theory that could bias memeticists to work on the ontology of meme units as opposed to hypotheses testing, which was adopted by the gene-culture scholars. I trace this problem back to the diachronic development of memetics to its origin in the gene-centered anti-group-selectionist argument of George C. Williams and Richard Dawkins. The strict adoption of this argument predisposed memeticists with the a priori idea that there is no evolution without discrete units of selection, which in turn, made them dependent on the principal separation of biological and memetic fitness. This separation thus prevented memeticists from accepting an adaptationist view of culture which, on the contrary, allowed gene-culture theorists to attract more scientists to test the hypotheses, creating the historical success of the gene-culture coevolution theory.

Making drugs out of sunlight and ‘thin air’: an emerging synergy of synthetic biology and natural product chemistry

Nature has long served as a rich source of structurally diverse small organic molecules with medicinally relevant biological activities. Despite the historical success of these so-called natural products, the enthusiasm of big pharma to explore these compounds as leads in drug design has waxed and waned. A major contributor to this is their often inherent structural complexity. Such compounds are difficult (often impossible) to access synthetically, a hurdle that can stifle lead development and hinder sustainable large-scale production of promising leads for clinical evaluation. However, in recent years, an emerging synergy between synthetic biology and natural product chemistry offers the potential for a renaissance in our ability to access natural products for drug discovery and development. Advances in genome sequencing, bioinformatics and the maturing of heterologous expression platforms are increasing, enabling the study, and ultimately, the manipulation of plant biosynthetic pathways. The triterpenes are one of the most structurally diverse families of natural products and arguably one of the most underrepresented in the clinic. The plant kingdom is the richest source of triterpene diversity, with >20,000 triterpenes reported so far. Transient expression of genes for candidate enzymes and pathways in amenable plant species is emerging as a powerful and rapid means of investigating and harnessing the plant enzymes involved in generating this diversity. Such platforms also have the potential to serve as production systems in their own right, with the possibility of upscaling these discoveries into commercially useful products using the same overall basic procedure. Ultimately, the carbon source for generation of high-value compounds in plants is photosynthesis. Therefore, we could, with the help of plants, be producing new medicines out of sunlight and ‘thin air’ in green factories in the not too distant future.

LGBTQ State Legislative Candidates in an Era of Backlash

In 2017, transgender woman Danica Roem stunned political observers in Virginia by unseating a long-time anti-LGBTQ legislator from a conservative district in the Virginia House of Delegates.1 She was the first openly transgender person elected and seated to a state legislature. Delegate Roem’s election was historic in LGBTQ political representation, but it also occurred in a period when backlash against the LGBTQ community seemed to be growing (Taylor, Lewis, and Haider-Markel 2018). These two threads led us to ask: How are LGBTQ candidates achieving historic successes even as forces seem mobilized against them?

Ecological quality of a forest in a state of succession based on structural parameters: A case study in an evergreen Amazonian-Andean forest, Ecuador

The evergreen forests of the Ecuadorian Amazon Region are altered by anthropogenic and natural factors. This provokes the need to look for tools that facilitate decision-making in support of restoration. We characterized the ecological structure and distribution of an evergreen Amazonian-Andean forest in the upper Puyo River micro-basin as a base for establishing an ecological quality index. The inventory was assessed using transects 0.1 ha (10 m × 100 m), registering the species with diameters at 1.30 m height ≥10 cm. We encountered a high degree of richness (30 families, 65 species and 322 individuals). The structural parameters indicated the predominance of a heterogeneous forest, with characteristics belonging to disturbed forests. A non-continuous vertical distribution pattern was found, determined by 78% of the species in a single stratum. The mixing ratio resulted in a higher proportion (1:5) for the lower class. The species Wettinia maynensis, Alchornea glandulosa, Miconia splendens, Piptocoma discolor and Inga velutina had the highest ecological value. The principal components analysis distinguished the abundance of species that had a high correlation with the sites and a distinct pattern was found in transect three. We developed the Structural Ecological Quality Index, which considers the social position of various species as well as their ecological importance, to reflect alterations in structural parameters. Abundance was concentrated in the 10–20 m strata (10–20 cm diameter class), which showed the presence of disturbance indicator species and a low ecological value. This indicated the real value of the historical succession of the forest, thus we recommend carrying out a restoration of this important reservoir.

Strategies and barriers to achieving the goal of Finland’s tobacco endgame

ObjectivesFinland boldly legislated the end of tobacco use in its 2010 Tobacco Act, and subsequently expanded the goal in 2016 to eradicate other nicotine-containing products. This study explored stakeholders’ perceptions...

An evaluational study: the perception of mother about routine immunization attending anganwadi centre in urban Hapur, Uttar Pradesh

Background: Immunization is the most powerful, safe and cost-effective measures for prevention/control of a number of diseases. The historical success of eradicating the dreaded disease, Smallpox, prompted World Health Organization (WHO) to ask its member countries to launch immunization against six vaccine preventable diseases in its national immunization schedule because unequivocal knowledge and practices helps to develop positive attitude towards vaccination and thus their contribution to vaccination. It helps to reduce the burden of dreadful infectious diseases, which are best controlled by vaccination. Poor maternal knowledge likely to results in partial immunization coverage or nill immunization coverage in children.Methods: Total 256 mother with children of aged 12-60 months were interviewed during four months duration, for the study. During the survey, 256 mothers having children between 12-60 months were interviewed through a pre-tested semi-structured questionnaire.Results: 97.08 mothers knew that immunization is to be started at birth, 39% of mothers knew that OPV protects against polio. All the mothers had received T.T during pregnancy as per schedule (93%) and 99% had received 2 doses. Maximum mother reported that information was received by ASHA/AWW.Conclusions: According to source of information the IEC activities should be increased and to improve the level of knowledge among mother of under five children.

Cultural and Historical succession of India from Vedic Period to Post Partition: River of Fire

Cultural and Historical succession of India from Vedic Period to Post Partition: River of Fire

Negotiating independence. Switzerland in 1647–48: Johann Rudolf Wettstein, mayor of the state (canton) of Basel City and negotiator for the Swiss Confederation

Cet article relate l’histoire de la négociation entreprise par M. Rudolf Wettstein, maire de Bâle, qui a pu obtenir du Saint-Empire germanique, lors des négociations qui aboutiront au Traité de Westphalie au 17 ème siècle, l’indépendance de la Confédération suisse. L’auteur fait d’abord le récit du déroulement et de la conclusion des négociations ; elles ont impliqué des négociations internationales multi-acteurs en Westphalie et des négociations internes multi-acteurs au sein de la Confédération suisse. Les concepts majeurs en théorie de la négociation sont ensuite mobilisés pour tenter de donner un sens à l’approche de Wettstein dans cette négociation pour l’indépendance. L’article se termine par une proposition visant à renforcer la théorisation et fournit des suggestions de concepts pour mieux saisir les négociations multi-acteurs.

The Annual Review of Applied Linguistics at 40: Looking Back and Moving Ahead

AbstractIt is a privilege to be Editor-in-Chief of the Annual Review of Applied Linguistics in 2020 as it celebrates its 40th year. This is my fifth issue as Editor. I will begin this short introduction by paying tribute, with the help of Bill Grabe (Northern Arizona University), to the founding editor of the journal, Robert Kaplan (1929–2020). Without Robert Kaplan, none of us would be reading these pages. We will then turn to some comments from each of the previous editors on a few of the highlights of their time editing the journal, along with words for the future. After this, I will describe some recent updates, go through a few of the historical successes of the journal, and then turn to the contents of the exciting current issue, “Looking back and moving ahead.”