According to luck egalitarianism, it is unjust if some are worse off than others through no fault or choice of their own. The most common criticism of luck egalitarianism is the ‘harshness ...objection’, which states that luck egalitarianism allows for too harsh consequences, as it fails to provide justification for why those responsible for their bad fate can be entitled to society's assistance. It has largely gone unnoticed that the harshness objection is open to a number of very different interpretations. We present four different interpretations of the harshness objection in which the problem pertains to counterintuitive implications, badness of outcome, disproportionality, or inconsistency, respectively. We analyse and discuss appropriate luck egalitarian replies. Disentangling these different versions clarifies what is at the heart of this dispute and reveals the point of the harshness objection. We conclude that only the inconsistency version involves a durable problem for luck egalitarianism.
Pandemic prioritarianism Nielsen, Lasse
Journal of medical ethics,
04/2022, Letnik:
48, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Prioritarianism pertains to the generic idea that it matters more to benefit people, the worse off they are, and while prioritarianism is not uncontroversial, it is considered a generally plausible ...and widely shared distributive principle often applied to healthcare prioritisation. In this paper, I identify social justice prioritarianism, severity prioritarianism and age-weighted prioritarianism as three different interpretations of the general prioritarian idea and discuss them in light of the effect of pandemic consequences on healthcare priority setting. On this analysis, the paper arrives at the following three conclusions: (1) that we have strong prioritarian reasons for special concern about the vulnerable and socially disadvantaged in reference to pandemic effects, (2) that severity of illness is an important factor in identifying the worse off in priority setting but that this must not over-ride the special priority to the socially disadvantaged and (3) that the maximisation rationale of the age-weighted view runs against the core prioritarian idea, and the age-weighted prioritarianism is thus unfitting as a prioritarian response to the COVID-19 case.
Semaglutide is a glucagon-like peptide-1 analogue (GLP-1) approved for once-weekly (OW) subcutaneous treatment of type 2 diabetes (Ozempic®). This randomised, double-blind, placebo-controlled, ...13-week trial assessed the pharmacokinetics, safety and tolerability of OW semaglutide in healthy male and female Chinese subjects. A total of 36 subjects were randomised to 0.5 mg (n=12) or 1.0 mg (n=12) OW semaglutide, or corresponding volumes of placebo (n=12). The primary endpoint was steady-state semaglutide exposure (AUC0 168h area under the curve over a dosing interval). Semaglutide exposure at steady state (see Figure) was consistent with dose-proportionality. Treatment ratios (1.0 mg/0.5 mg) were: AUC0-168h: 1.99, and Cmax: 1.94. Accumulation was consistent with the half-life (∼1 week). In this trial, treatment with OW semaglutide was well tolerated, consistent with the GLP-1 class. The PK profile in Chinese subjects was consistent with previous trials. The most common adverse events were gastrointestinal events. NCT03288740.
Disclosure
A. Shi: None. P. Xie: None. L.L. Nielsen: None. T.V. Skjoeth: Employee; Self; Novo Nordisk A/S. X. He: None. S.P. Haugaard: Employee; Self; Novo Nordisk A/S.
Funding
Novo Nordisk A/S
Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown ...to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy. Here we compared peanut allergen delivery
the oral, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes for the prevention of peanut allergy in Brown Norway (BN) rats.
BN rats were administered PBS or three different doses of peanut protein extract (PPE)
either oral IT (OIT), SLIT, IGIT or SCIT followed by intraperitoneal (IP) injections of PPE to assess the protection from peanut sensitisation. The development of IgE and IgG1 responses to PPE and the major peanut allergens were evaluated by ELISAs. The clinical response to PPE was assessed by an ear swelling test (EST) and proliferation was assessed by stimulating splenocytes with PPE.
Low and medium dose OIT (1 and 10 mg) and all doses of SCIT (1, 10, 100 µg) induced sensitisation to PPE, whereas high dose OIT (100 mg), SLIT (10, 100 or 1000 µg) or IGIT (1, 10 and 100 mg) did not. High dose OIT and SLIT as well as high and medium dose IGIT prevented sensitisation from the following IP injections of PPE and suppressed PPE-specific IgE levels in a dose-dependent manner. Hence, administration of peanut protein
different routes confers different risks for sensitisation and protection from peanut allergy development. Overall, the IgE levels toward the individual major peanut allergens followed the PPE-specific IgE levels.
Collectively, this study showed that the preventive effect of allergen-specific IT is determined by the interplay between the specific site of PPE delivery for presentation to the immune system, and the allergen quantity, and that targeting and modulating tolerance mechanisms at specific mucosal sites may be a prophylactic strategy for prevention of peanut allergy.
Criegee Intermediates React with Ozone Kjaergaard, Henrik G; Kurtén, Theo; Nielsen, Lasse B ...
The journal of physical chemistry letters,
08/2013, Letnik:
4, Številka:
15
Journal Article
Recenzirano
We have investigated the reaction of the one-carbon stabilized Criegee intermediate (H2COO, formaldehyde oxide) with ozone, theoretically, using high level coupled cluster ab initio methods. Key to ...the reactivity of the Criegee intermediate with ozone is the strongly exothermic formation of an intermediate consisting of five oxygen and one carbon atoms (H2CO5) in a six-membered ring structure. This intermediate proceeds via a spin-allowed route over two transition states with low energy barriers to form molecular oxygen and formaldehyde. The reaction may contribute to the loss of these biradicals in the atmosphere.
Substantial amounts of annual radiocarbon (14C) data have recently been produced with the purpose of increasing the time resolution of 14C records used for constructing the calibration curve and for ...studying the occurrence of abrupt cosmic-ray events. In this study, we investigate if it is possible to resolve sub-annual scale changes in the atmospheric 14C content by measuring radiocarbon in early-wood and late-wood fractions from Danish oak. The tree-ring samples span the period 1954–1970 CE, hereby covering the peak of the bomb pulse. A least squares test comparing the atmospheric 14C content and the new sub-annual 14C record from Danish tree rings reveals that by measuring early-wood and late-wood fractions, it may be possible to resolve sub-annual variations in past atmospheric 14C levels.
Interactions between planktonic organisms, such as detection of prey, predators, and mates, are often mediated by fluid signals. Consequently, many plankton predators perceive their prey from the ...fluid disturbances that it generates when it feeds and swims. Zooplankton should therefore seek to minimize the fluid disturbance that they produce. By means of particle image velocimetry, we describe the fluid disturbances produced by feeding and swimming in zooplankton with diverse propulsion mechanisms and ranging from 10-µm flagellates to greater than millimeter-sized copepods. We show that zooplankton, in which feeding and swimming are separate processes, produce flow disturbances during swimming with a much faster spatial attenuation (velocity u varies with distance r as u ∝ r ⁻³ to r ⁻⁴) than that produced by zooplankton for which feeding and propulsion are the same process (u ∝ r ⁻¹ to r ⁻²). As a result, the spatial extension of the fluid disturbance produced by swimmers is an order of magnitude smaller than that produced by feeders at similar Reynolds numbers. The “quiet” propulsion of swimmers is achieved either through swimming erratically by short-lasting power strokes, generating viscous vortex rings, or by “breast-stroke swimming.” Both produce rapidly attenuating flows. The more “noisy” swimming of those that are constrained by a need to simultaneously feed is due to constantly beating flagella or appendages that are positioned either anteriorly or posteriorly on the (cell) body. These patterns transcend differences in size and taxonomy and have thus evolved multiple times, suggesting a strong selective pressure to minimize predation risk.
Age rationing is a central issue in the health care priority‐setting literature, but it has become ever more salient in the light of the Covid‐19 outbreak, where health authorities in several ...countries have given higher priority to younger over older patients. But how is age rationing different under outbreak circumstances than under normal circumstances, and what does this difference imply for ethical theories? This is the topic of this paper. The paper argues that outbreaks such as that of Covid‐19 involve special circumstances that change how age should influence our prioritization decisions, and that while this shift in circumstances poses a problem for consequentialist views such as utilitarianism and age‐weighted consequentialism, contractualism is better equipped to cope with it. The paper then offers a contractualist prudential account of age rationing under outbreak circumstances.
Some phagotrophic organisms can retain chloroplasts of their photosynthetic prey as so-called kleptochloroplasts and maintain their function for shorter or longer periods of time. Here we show for ...the first time that the dinoflagellate Dinophysis acuta takes control over "third-hand" chloroplasts obtained from its ciliate prey Mesodinium spp. that originally ingested the cryptophyte chloroplasts. With its kleptochloroplasts, D. acuta can synthesize photosynthetic as well as photoprotective pigments under long-term starvation in the light. Variable chlorophyll fluorescence measurements showed that the kleptochloroplasts were fully functional during 1 month of prey starvation, while the chlorophyll a-specific inorganic carbon uptake decreased within days of prey starvation under an irradiance of 100 μmol photons m(-2) s(-1). While D. acuta cells can regulate their pigmentation and function of kleptochloroplasts they apparently lose the ability to maintain high inorganic carbon fixation rates.
Hydrodynamics of microbial filter feeding Nielsen, Lasse Tor; Asadzadeh, Seyed Saeed; Dölger, Julia ...
Proceedings of the National Academy of Sciences - PNAS,
08/2017, Letnik:
114, Številka:
35
Journal Article
Recenzirano
Odprti dostop
Microbial filter feeders are an important group of grazers, significant to the microbial loop, aquatic food webs, and biogeochemical cycling. Our understanding of microbial filter feeding is poor, ...and, importantly, it is unknown what force microbial filter feeders must generate to process adequate amounts of water. Also, the trade-off in the filter spacing remains unexplored, despite its simple formulation: A filter too coarse will allow suitably sized prey to pass unintercepted, whereas a filter too fine will cause strong flow resistance. We quantify the feeding flow of the filter-feeding choanoflagellate Diaphanoeca grandis using particle tracking, and demonstrate that the current understanding of microbial filter feeding is inconsistent with computational fluid dynamics (CFD) and analytical estimates. Both approaches underestimate observed filtration rates by more than an order of magnitude; the beating flagellum is simply unable to draw enough water through the fine filter. We find similar discrepancies for other choanoflagellate species, highlighting an apparent paradox. Our observations motivate us to suggest a radically different filtration mechanism that requires a flagellar vane (sheet), something notoriously difficult to visualize but sporadically observed in the related choanocytes (sponges). A CFD model with a flagellar vane correctly predicts the filtration rate of D. grandis, and using a simple model we can account for the filtration rates of other microbial filter feeders. We finally predict how optimum filter mesh size increases with cell size in microbial filter feeders, a prediction that accords very well with observations. We expect our results to be of significance for small-scale biophysics and trait-based ecological modeling.
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