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What do corporations do?
No full textCorporations act as entities addressing the world with a single face and voice, with the law resorting to metaphors such as the “person” (persona) and “body” (corpore) to present the group as an entity distinct from its members. Four historic models of group action can provide an added functional analysis in grappling with the role of the corporation: the “cathedral” built by self-regulating guilds and societies; the “factory” resting on division of labour and hierarchical organization; the “bazaar” of adjoining enterprises providing some level of market integration between traders; and the “commune” resting on personalised bonds and common purposes. These ideal types can hybridize across time, and we should avoid exclusive focus on the factory type 2. All forms are affected by co-ordination problems arising whenever members of any group take joint decisions, or set up a deliberative system for forming judgments preparatory to taking decisions. A group can be said to attain corporate status when it must function as a univocal entity owning its actions as a condition of survival; the corporation then behaves and thinks as an agent or entity distinct from its membership. In order to act effectively as a singular agent, the corporation must develop techniques to gather and process information attained by its agents, much of which will be predictions of the conduct of external agents. The novel argument presented here is that the corporation in each of the four ideal types exists to cultivate and embody common knowledge, though each of the types will aggregate and use information differently. Common knowledge is here used as a term of art derived from philosophy of mind and rational choice theory, and involves not only ‘nested’ knowledge of the world (we know certain facts and we know of each other’s knowledge state regarding those facts) but also conventions governing interactions between rational actors mutually anticipating each other’s actions. Preceding the conceptual analysis, an introductory section provides a case study of problems of group action and knowledge-sharing in an historically important and now-troubled corporation, namely the Boeing Company of Seattle
Pneumococcal density and respiratory co-detection in severe pediatric pneumonia in Laos
Get PDFThere is growing evidence on the importance of bacterial/viral interaction in the course of pneumonia. In Laos, no study has investigated respiratory pathogen co-detection. We conducted a study at Mahosot Hospital in Vientiane to determine whether bacterial/viral co-detection and pneumococcal density are associated with severe pneumonia. Between December 2013 and December 2016, 934 under 5 years old hospitalized children with ARI were enrolled. Swabs from the upper respiratory tract were collected and analyzed by real-time PCR. The most common co-detected microorganisms were Streptococcus pneumoniae/Haemophilus influenzae (24%), Respiratory Syncytial Virus (RSV)/S. pneumoniae (12%) and RSV/H. influenzae (16%). Pneumococcal density was 4.52 times higher in influenza virus positive participants. RSV/S. pneumoniae and RSV/H. influenzae co-detections were positively associated with severe pneumonia in univariate analysis (OR 1.86, 95%CI:1.22–2.81, p = 0.003 and OR 2.09, 95%CI:1.46-3.00), but not confirmed in adjusted analysis (aOR 0.72, 95%CI:0.38–1.6, p = 0.309 and aOR 1.37, 95%CI:0.73–2.58). In RSV positive patients, there was no association between pneumococcal density and severe pneumonia. Our findings confirmed an association between pneumococcal density and influenza but not RSV severe pneumonia in young children. Results highlight the complexity of the interaction of viral/bacterial pathogens, which might not have a simple synergistic action in the evolution of pneumonia
The mental health impact of the climate and ecological crisis on vulnerable populations in Africa
No full textScientists have been predicting the severe impacts of climate change for decades, and today these threats have intensified, with climate events pushing temperatures, sea levels and biodiversity loss to record extremes. This review examines the impact of climate change on mental health in vulnerable populations residing in Africa. Medline, Embase, Ovid, APA PsycINFO, Global Health were searched for studies published after 2007 researching the psychological impact of climate change on vulnerable African populations. Studies were screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and results were reviewed using a narrative synthesis approach. Twenty-one articles, including 36,425 participants, were analysed. The results suggest that women, young people, farmers, migrants, people living in rural areas and survivors of climate-related traumatic experiences (such as extreme weather events) are all vulnerable to mental health impacts caused by the climate crisis. Future research is needed in African countries which have not yet been studied, including island nations. Further high-quality research is required to establish longitudinal impacts of the climate crisis and to explore the impacts on vulnerable groups which are, as yet, neglected in the research, including, e.g., ethnic minorities, indigenous groups and LGBTQ+ communities
Resolving the nature and putative nebular emission of GS9422: an obscured AGN without exotic stars
Get PDFUnderstanding the sources that power nebular emission in high-redshift galaxies is fundamentally important not only for shedding light on to the drivers of reionization, but to constrain stellar populations and the growth of black holes. Here, we focus on an individual object, GS9422, a galaxy at with exquisite data from the JWST Advanced Deep Extragalactic Survey (JADES), JWST Extragalactic Medium-band Survey (JEMS), and First Reionization Epoch Spectroscopically Complete Observations (FRESCO) surveys, including 14-band JWST/NIRCam photometry and deep NIRSpec prism and grating spectroscopy. We map the continuum emission and nebular emission lines across the galaxy on 0.2-kpc scales. GS9422 has been claimed to have nebular-dominated continuum and an extreme stellar population with top-heavy initial mass function. We find clear evidence for different morphologies in the emission lines, the rest-ultraviolet and rest-optical continuum emission, demonstrating that the full continuum cannot be dominated by nebular emission. While multiple models reproduce the spectrum reasonably well, our preferred model with a type-2 active galactic nucleus (AGN) and local damped Ly (DLA) clouds can explain both the spectrum and the wavelength-dependent morphology. The AGN powers the off-planar nebular emission, giving rise to the Balmer jump and the emission lines, including Ly, which therefore does not suffer DLA absorption. A central, young stellar component dominates the rest-UV emission and – together with the DLA clouds – leads to a spectral turn over. A disc-like, older stellar component explains the flattened morphology in the rest-optical continuum. We conclude that GS9422 is consistent with being a normal galaxy with an obscured, type-2 AGN – a simple scenario, without the need for exotic stellar populations
Tocilizumab, sarilumab and anakinra in critically ill patients with COVID-19: a randomised, controlled, open-label, adaptive platform trial
Get PDFIntroduction: Tocilizumab improves outcomes in critically ill patients with COVID-19. Whether other immune-modulator strategies are equally effective or better is unknown. Methods: We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients. In this ongoing, adaptive platform trial in 133 sites in 9 countries, we randomly assigned patients with allocation ratios dependent on the number of interventions available at each site. The primary outcome was an ordinal scale combining in-hospital mortality (assigned –1) and days free of organ support to day 21 in survivors. The trial used a Bayesian statistical model with predefined triggers for superiority, inferiority, efficacy, equivalence or futility. Results: Of 2274 critically ill participants enrolled between 25 March 2020 and 10 April 2021, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were 7 (IQR –1, 16), 9 (IQR –1, 17), 0 (IQR –1, 15) and 0 (IQR –1, 15) for tocilizumab, sarilumab, anakinra and control, respectively. Median adjusted ORs were 1.46 (95% credible intervals (CrI) 1.13, 1.87), 1.50 (95% CrI 1.13, 2.00) and 0.99 (95% CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra relative to control, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared with control. All treatments appeared safe. Conclusions: In critically ill patients with COVID-19, tocilizumab and sarilumab have equivalent effectiveness at reducing duration of organ support and death. Anakinra is not effective in this population. Trial registration number: NCT02735707
The role of orphan receptor GPR84 in macrophage biology and inflammation
Get PDFGPR84 is a Class A orphan GPCR expressed primarily by innate immune cells. Despite significant advances in our understanding of GPR84 in the past 23 years the endogenous agonist(s) remain unknown. Current evidence suggests a primary role for this receptor in inflammation, though its pathophysiological role and the best strategy to exploit its activity therapeutically also remain unknown. This is true at both the physiological level, exemplified by disease models and clinical studies, but also at the molecular level, exemplified by a lack of understanding of downstream pathways and their relationship to cellular function. Surrogate agonists acting at this receptor have been shown to promote the mobilisation of inflammatory mediators, chemotaxis, and phagocytosis in a cell and context-dependent manner. However, the influence of agonist bias via the transducer proteins Gαi and β-arrestin-2 on these cellular responses are unclear. The development of chemical and biological tools to study the function of GPR84 are described herein, including two probes suitable for use in vivo and recombinant cell lines that phenocopy the response of macrophages. A detailed assessment of the signalling and kinetics of responses elicited by the agonists 6-OAU and DL-175 revealed that DL-175 exhibits a delayed impedance response, a delayed and suppressed activation of Akt, and an impaired ability to internalise the receptor. Finally, through the development of a screening set of chemically and biologically diverse agonists a relationship between agonist desensitisation potency and cAMP potency was found, but only a weak relationship between level of internalisation and level of bias. The lack of strong explanatory correlations between compounds in each assay highlights the potential to ‘dial’ receptor signalling in or out based on chemical structure. This work has furthered our molecular understanding of GPR84 signalling and supports research for the development of novel compounds with novel properties
Mining under empire: exploiting the metal resources of Roman Dacia
No full textThis thesis explores how the Romans managed the metal resources of Roman Dacia, and the impact that the advent of Roman rule had on mining in the province. Roman Dacia has long been a byword in the scholarly literature for its mineral wealth, but modern archaeological research on the mining remains has thus far been lacking until the excavations at Roșia Montană took place between 1999 and 2013. Through a synthesis of the archival literature and the latest results from the Roșia Montană excavations, this project demonstrates the vibrancy and diversity of mining in Dacia, arguing that the Romans were able to exploit the metal deposits of Dacia more effectively and on a larger scale than their predecessors through the application of mining technology and experience acquired elsewhere in the Empire. It illustrates how Roșia Montană was probably the foremost mining site in Dacia, but that the Romans also identified and exploited almost all the known mining regions in the province. The diversity of their methods allowed for adaptation to local circumstances both in terms of the geological and administrative needs of specific mining sites. To supplement the secondary research, ground-truthing to verify possible hydraulic-mining remains identified through satellite imagery was also undertaken. Key results of this study include establishing type-sites for hard-rock mining and hydraulic mining at Roșia Montană, and at Bucium and Pianu de Sus respectively, to aid in the identification of other similar workings in Dacia. This thesis also makes available, for the first time, the fullest treatment of the mines of Roman Dacia in English and provides a gazetteer of sites for future work
Global vegetation dynamics under decreased terrestrial water storage: insights into water stress response
Get PDFTerrestrial water storage (TWS) plays a critical role in regulating global water-energy budget, significantly influencing water availability and carbon sequestration dynamics. However, how decreased TWS affect terrestrial carbon assimilation under climate change remains poorly understood. This study explores the influence of TWS on vegetation productivity across diverse ecosystems by synthesizing satellite observations, reanalysis datasets, field measurements, and long-term TWS reconstructions. We apply a supervised machine learning model and path analysis to examine how dominant water-heat factors—such as soil moisture, vapor pressure deficit, precipitation and temperature—regulate vegetation photosynthesis under varying levels of water stress. Moreover, we employ a large set of hydro-climate models to project future TWS scenarios, and quantify their impacts on vegetation productivity in a warming climate. Our findings indicate that intensifying drought conditions, indicated by decreased TWS, lead to increasingly severe reductions in vegetation productivity, particularly in water-limited regions. The integrated model framework projects that climate warming could significantly worsen drought impacts on vegetation productivity. As drought severity escalates from moderate drought to exceptional drought, the global average gross primary productivity decreases from -3.20 gm−2day−1to -7.10gm−2day−1under low carbon emission scenarios. These insights highlight the critical need to develop robust strategies to enhance ecosystem resilience against worsening drought conditions, underscoring a key aspect of climate adaptation efforts
The causal relevance of body composition to disease: analyses of the UK Biobank and the FinnGen Study
No full textBackground
BMI is the most commonly used measure of adiposity and body composition, but it does not differentiate between fat mass (FM) and fat-free mass (FFM). The primary aim of this thesis was to assess the causal relevance of FM and FFM to a wide range of diseases, using Mendelian randomisation (MR) methods. A secondary aim was to identify proteins with the potential to be targets of drugs for adiposity reduction.
Methods
Following a systematic review, two-sample MR analyses of FM and FFM and 800 diseases were conducted using data on the two exposures from de novo genome-wide association studies (GWAS) of 400K UK Biobank (UKB) participants of “White British” ancestry and summary statistics from GWAS of the outcomes conducted using samples of up to 412K “Finnish-ancestry” FinnGen study participants. Additionally, proteomic data from the UKB (n = 35K) were used in cis MR and colocalisation analyses to identify proteins that are causally relevant to FM and may have the potential to be drug targets. A variety of sensitivity analyses were performed to assess the robustness of the findings.
Results
Eighty-seven robust, positive associations were identified between genetically predicted FM and diseases across 13 disease categories, including cardiovascular, digestive, genitourinary, metabolic, and respiratory diseases (and one inverse association). Sixty-four of these were previously unreported in MR studies of FM, including, for instance, positive associations with hypertensive heart disease, chronic kidney disease, cholecystitis, asthma, chronic obstructive pulmonary disease, and chronic lower respiratory diseases. Genetically predicted FFM was found to have robust, positive associations with 26 diseases, including multiple diseases of the heart and musculoskeletal diseases, and seven robust, inverse associations, such as with metabolic disorders, depression, and complications of labour and delivery (24 of these were novel). Cis MR analyses identified 21 proteins as causally relevant to FM; evidence of colocalisation was also found for five of the proteins: AGER, CRIM1, DNER, NEFL, and PRRT3. Two of the proteins – AGER and ADM – are targets of drugs investigated in advanced-stage clinical trials for indications not closely related to adiposity.
Conclusion
The findings provide evidence of the causal relevance of FM to a wide range of diseases, as well as of FFM to a smaller but still considerable set of diseases (with some inverse relationships). They also point to several proteins as potential drug targets for FM reduction. The results suggest public health strategies, clinical assessments of disease risk, and treatments could benefit from distinguishing between FM and FFM and focusing on the appropriate body component. The findings may also inform future trials and other research on the expected effects of interventions addressing body composition, as well as additional studies on the identified proteins as drug targets
Experimental tests of invariant set theory
Get PDFWe identify points of difference between Invariant Set Theory and standard quantum theory, and show that these lead to noticeable differences in predictions between the two theories. We design a number of experiments to test which of these predictions corresponds to our world. If these experiments were undertaken, they would allow us to investigate whether standard quantum theory or invariant set theory best describes reality. These tests can also be deployed on theories sharing similar properties (e.g., Penrose’s gravitational collapse theory)