Ethical frameworks should be applied to computational modelling of infectious disease interventions

This perspective is part of an international effort to improve epidemiological models with the goal of reducing the unintended consequences of infectious disease interventions. The scenarios in which models are applied often involve difficult trade-offs that are well recognised in public health ethics. Unless these trade-offs are explicitly accounted for, models risk overlooking contested ethical choices and values, leading to an increased risk of unintended consequences. We argue that such risks could be reduced if modellers were more aware of ethical frameworks and had the capacity to explicitly account for the relevant values in their models. We propose that public health ethics can provide a conceptual foundation for developing this capacity. After reviewing relevant concepts in public health and clinical ethics, we discuss examples from the COVID-19 pandemic to illustrate the current separation between public health ethics and infectious disease modelling. We conclude by describing practical steps to build the capacity for ethically aware modelling. Developing this capacity constitutes a critical step towards ethical practice in computational modelling of public health interventions, which will require collaboration with experts on public health ethics, decision support, behavioural interventions, and social determinants of health, as well as direct consultation with communities and policy makers

Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7

Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arteries. The objective of this study was to examine the potential toxicity of synthetic MK-7 in BomTac:NMRI mice and in Sprague-Dawley rats. In an acute oral toxicity test, mice were administered a single oral dose of 2000 mg/kg body weight (limit dose) and no toxicity was observed during the 14-day observation period. In the subchronic oral toxicity test in rats, animals were administered MK-7 for 90 days by gavage at the following doses: 0 (vehicle control, corn oil), 2.5, 5, and 10 mg/kg body weight/day. All generated data, including clinical observations, ophthalmology, clinical pathology, gross necropsy, and histopathology, revealed no compound-related toxicity in rats. Any statistically significant findings in clinical pathology parameters and/or organ weights noted were considered to be within normal biological variability. Therefore, under the conditions of this experiment, the median lethal dose (LD50) of MK-7 after a single oral administration in mice was determined to be greater than the limit dose level of 2000 mg/kg body weight. The no observed adverse effect level (NOAEL) of MK-7, when administered orally to rats for 90 days, was considered to be equal to 10 mg/kg body weight/day, the highest dose tested, based on lack of toxicity during the 90-day study period

Double hadron leptoproduction in the nuclear medium

First measurement of double-hadron production in deep-inelastic scattering has been measured with the HERMES spectrometer at HERA using a 27.6 GeV positron beam with deuterium, nitrogen, krypton and xenon targets. The influence of the nuclear medium on the ratio of double-hadron to single-hadron yields has been investigated. Nuclear effects are clearly observed but with substantially smaller magnitude and reduced $A$-dependence compared to previously measured single-hadron multiplicity ratios. The data are in fair agreement with models based on partonic or pre-hadronic energy loss, while they seem to rule out a pure absorptive treatment of the final state interactions. Thus, the double-hadron ratio provides an additional tool for studying modifications of hadronization in nuclear matter

Quark helicity distributions in the nucleon for up, down, and strange quarks from semi--inclusive deep--inelastic scattering

Polarized deep--inelastic scattering data on longitudinally polarized hydrogen and deuterium targets have been used to determine double spin asymmetries of cross sections. Inclusive and semi--inclusive asymmetries for the production of positive and negative pions from hydrogen were obtained in a re--analysis of previously published data. Inclusive and semi--inclusive asymmetries for the production of negative and positive pions and kaons were measured on a polarized deuterium target. The separate helicity densities for the up and down quarks and the anti--up, anti--down, and strange sea quarks were computed from these asymmetries in a ``leading order'' QCD analysis. The polarization of the up--quark is positive and that of the down--quark is negative. All extracted sea quark polarizations are consistent with zero, and the light quark sea helicity densities are flavor symmetric within the experimental uncertainties. First and second moments of the extracted quark helicity densities in the measured range are consistent with fits of inclusive data

Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction

Evidence for a narrow baryon state is found in quasi-real photoproduction on a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1 (syst) MeV. Depending on the background model,the naive statistical significance of the peak is 4--6 standard deviations and its width may be somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s)) pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed in the pK^+ invariant mass distribution. The absence of such a signal indicates that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure

Unusual Regulation of a Leaderless Operon Involved in the Catabolism of Dimethylsulfoniopropionate in Rhodobacter sphaeroides

Rhodobacter sphaeroides strain 2.4.1 is a widely studied bacterium that has recently been shown to cleave the abundant marine anti-stress molecule dimethylsulfoniopropionate (DMSP) into acrylate plus gaseous dimethyl sulfide. It does so by using a lyase encoded by dddL, the promoter-distal gene of a three-gene operon, acuR-acuI-dddL. Transcription of the operon was enhanced when cells were pre-grown with the substrate DMSP, but this induction is indirect, and requires the conversion of DMSP to the product acrylate, the bona fide co-inducer. This regulation is mediated by the product of the promoter-proximal gene acuR, a transcriptional regulator in the TetR family. AcuR represses the operon in the absence of acrylate, but this is relieved by the presence of the co-inducer. Another unusual regulatory feature is that the acuR-acuI-dddL mRNA transcript is leaderless, such that acuR lacks a Shine-Dalgarno ribosomal binding site and 5′-UTR, and is translated at a lower level compared to the downstream genes. This regulatory unit may be quite widespread in bacteria, since several other taxonomically diverse lineages have adjacent acuR-like and acuI-like genes; these operons also have no 5′ leader sequences or ribosomal binding sites and their predicted cis-acting regulatory sequences resemble those of R. sphaeroides acuR-acuI-dddL

Symbolic meanings and e-learning in the workplace: The case of an intranet-based training tool

This article contributes to the debate on work-based e-learning, by unpacking the notion of ‘the learning context’ in a case where the mediating tool for training also supports everyday work. Users’ engagement with the information and communication technology tool is shown to reflect dynamic interactions among the individual, peer group, organizational and institutional levels. Also influential are professionals’ values and identity work, alongside their interpretations of espoused and emerging symbolic meanings. Discussion draws on pedagogically informed studies of e-learning and the wider organizational learning literature. More centrally, this article highlights the instrumentality of symbolic interactionism for e-learning research and explores some of the framework’s conceptual resources as applied to organizational analysis and e-learning design. </jats:p

Thyroid Hormone Signalling Genes Are Regulated by Photoperiod in the Hypothalamus of F344 Rats

Seasonal animals adapt their physiology and behaviour in anticipation of climate change to optimise survival of their offspring. Intra-hypothalamic thyroid hormone signalling plays an important role in seasonal responses in mammals and birds. In the F344 rat, photoperiod stimulates profound changes in food intake, body weight and reproductive status. Previous investigations of the F344 rat have suggested a role for thyroid hormone metabolism, but have only considered Dio2 expression, which was elevated in long day photoperiods. Microarray analysis was used to identify time-dependent changes in photoperiod responsive genes, which may underlie the photoperiod-dependent phenotypes of the juvenile F344 rat. The most significant changes are those related to thyroid hormone metabolism and transport. Using photoperiod manipulations and melatonin injections into long day photoperiod (LD) rats to mimic short day (SD), we show photoinduction and photosuppression gene expression profiles and melatonin responsiveness of genes by in situ hybridization; TSHβ, CGA, Dio2 and Oatp1c1 genes were all elevated in LD whilst in SD, Dio3 and MCT-8 mRNA were increased. NPY was elevated in SD whilst GALP increased in LD. The photoinduction and photosuppression profiles for GALP were compared to that of GHRH with GALP expression following GHRH temporally. We also reveal gene sets involved in photoperiodic responses, including retinoic acid and Wnt/ß-catenin signalling. This study extends our knowledge of hypothalamic regulation by photoperiod, by revealing large temporal changes in expression of thyroid hormone signalling genes following photoperiod switch. Surprisingly, large changes in hypothalamic thyroid hormone levels or TRH expression were not detected. Expression of NPY and GALP, two genes known to regulate GHRH, were also changed by photoperiod. Whether these genes could provide links between thyroid hormone signalling and the regulation of the growth axis remains to be investigated