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Why Do Different Forms of Knowledge Matter in Evidence-Based Drug Policy?
In the introduction to this special issue, the editors introduce the reader to research methodologies and analyses not commonly presented in mainstream health policy literature. Intersectional analysis, for example, is a means of drilling down into how the multiple social categories a person occupies (e.g., gender, class, ethnicity) may influence their experience of inequality. When an intersectional framework was applied to US Behavioral Risk Factor Surveillance System data in 2018 and 2019, for example, gender minority Blacks were identified as having distinctly poor health experiences compared with cisgender Black and other non-Black gender minority populations.1 Consequently, health policies and monitoring programs that purport to advance health equity must account for multiply marginalized populations such as these.Looking at drug policy through an intersectional lens reinforces the importance of macrolevel social determinants as they interact with meso and microlevel factors to influence drug harms and mediate policy and intervention effectiveness2 as well as the role of power in excluding certain perspectives, framings, forms of knowledge, and experience.3 Ethnographic, social-scientific, and community-based research methodologies challenge power imbalances by favoring the embodied knowledge of those with lived experience, knowledge gained by direct observation and study of the particular history and economic and political systems in a given location,2 as opposed to forms of professional expertise favored by public authorities seeking to govern society at a distance.
Journal Article
Improving homology modeling from low-sequence identity templates in Rosetta: A case study in GPCRs
As sequencing methodologies continue to advance, the availability of protein sequences far outpaces the ability of structure determination. Homology modeling is used to bridge this gap but relies on high-identity templates for accurate model building. G-protein coupled receptors (GPCRs) represent a significant target class for pharmaceutical therapies in which homology modeling could fill the knowledge gap for structure-based drug design. To date, only about 17% of druggable GPCRs have had their structures characterized at atomic resolution. However, modeling of the remaining 83% is hindered by the low sequence identity between receptors. Here we test key inputs in the model building process using GPCRs as a focus to improve the pipeline in two critical ways: Firstly, we use a blended sequence- and structure-based alignment that accounts for structure conservation in loop regions. Secondly, by merging multiple template structures into one comparative model, the best possible template for every region of a target can be used expanding the conformational space sampled in a meaningful way. This optimization allows for accurate modeling of receptors using templates as low as 20% sequence identity, which accounts for nearly the entire druggable space of GPCRs. A model database of all non-odorant GPCRs is made available at www.rosettagpcr.org . Additionally, all protocols are made available with insights into modifications that may improve accuracy at new targets.
Journal Article
Balkan syntax and (universal) principles of grammar
This book investigates morpho-syntactic convergences that characterize the languages of the Balkan Sprachbund: Balkan Slavic, Greek, Romanian, Albanian, Balkan Romani. Apart from new data, the volume features contributions within different theoretical frameworks (contact linguistics, functional linguistics, typology, areal linguistics, and generative grammar). -- Back cover
Book
Conflicting trends in violent crime measured by police recorded crime and the crime survey in England and Wales since 2010
Police recorded violent crime (PRC) and the Crime Survey of England and Wales (CSEW) show substantially different trends in the rates of violent crime according to the Office of National Statistics (ONS), with rates rising in police data and falling in survey data. Both the PRC and CSEW have suffered periods in which the UK Statistics Authority has withdrawn their quality approval as ‘national statistics’. This paper investigates a possible seven reasons for the disparity in the trend and volume of violent crime between the PRC and CSEW, with a focus on the processes of measurement deployed. The paper offers a new way to compare the methods and outcomes of the two data sources, by developing an ‘aligned’ data set to support comparison of trends in the PRC CSEW data since 2010. It analyses data from the PRC and from different sections of the CSEW, the main face-to-face module, the self-completion module on domestic abuse, and the children’s module asked of those aged 10–15 years. We offer new estimates of the volume and discussion on the trend in violent crime since 2010. We estimate that there were 5,164,983 violent crimes in 2022/3. This is significantly higher than the estimate provided by the ONS based on CSEW data. The estimate of the trend is uncertain, but challenges over-confidence in the assumption that it is declining. We conclude that improvements in police accuracy in recording crime explains part of the difference, and the exclusion from sampling of vulnerable groups by the CSEW another part, with the recent reduction in the survey’s response rate to 42% giving further quality concerns. We determine that the CSEW has always underestimated violent crime, and this has become visible now that police data has improved.
Journal Article
Can Ethics Exist Without God? A Thomistic Critique of James Sterba’s Axiomatic Morality
This essay explores the question: can we have an objective ethics without God? This question is raised by James Sterba, who argues in the affirmative. As an atheistic ethicist, Sterba is motivated to maintain an objective morality that is not based in theism and that can withstand the problems with Darwinism. Sterba examines what he sees as one of the most popular theistic attempts to ground human morality, viz., divine command theory. In rejecting both divine command theory and theism, Sterba offers what he believes can offer objective morality: a basic moral norm that all people should adhere to. This article examines Sterba’s criticism of divine command theory along with his own efforts at establishing an objective morality in what he considers a universal abstract principle. In the end, this article argues that Sterba’s axiomatic principle is unclear as to its ontological foundation as well as its causal efficacy in attempting to obligate objective human ethics. It will be argued that Sterba is correct about human nature being the locus of morality, but that atheism fails at providing human teleology to account for such morality.
Journal Article
Object location memories recruit distal CA1 and catecholaminergic inputs to proximodistal CA1
The hippocampus is thought to combine \"what\" and \"where\" information from the cortex so that objects and events can be represented within the spatial context in which they occur. Surprisingly then, these distinct types of information remain partially segregated in the output region of the hippocampus, area CA1. In this region, objects preferentially activate neurons in the distal segment (adjacent to the subiculum) while spatial locations are precisely represented by neurons in the proximal segment (adjacent to CA2). This difference likely results from distinct anatomical connections; proximal CA1 receives direct input from the medial entorhinal cortex (which encodes spatial context) whereas distal CA1 has reciprocal connections with the lateral entorhinal cortex (which encodes objects and events). Based on these findings, it has been proposed that CA1 contains two distinct representations; one that encodes the animal's spatial location and another that encodes objects that are present in the environment. The current study aimed to determine the role of distal CA1 in learning the location of objects in an environment. To do this, we first demonstrated that distal CA1 is more responsive (higher levels of c-Fos) to objects while proximal is spatially tuned. Further, as previous studies indicate that catecholamines can regulate CA1 activity, we lesioned the catecholaminergic inputs to CA1 and observed a reduction in c-Fos levels in both segments of CA1, and an impairment in object location memory 24h after training. Together, these findings indicate that processing object location in an environment recruits distal CA1 and catecholaminergic inputs to CA1.
Journal Article