Explicating ways of consensus-making in science and society: distinguishing the academic, the interface and the meta-consensus

In this chapter, we shed new light on the epistemic struggle between establishing consensus and acknowledging plurality, by explicating different ways of consensus-making in science and society and examining the impact hereof on their field of intersection, i.e. consensus conferences (in particular those organized by the National Institute of Health). We draw a distinction between, what we call, academic and interface consensus, to capture the wide appeal to consensus in existing literature. We investigate such accounts - i.e. from Miriam Solomon, John Beatty and Alfred Moore, and Boaz Miller - as to put forth a new understanding of consensus-making, focusing on the meta-consensus. We further defend how (NIH) consensus conferences enable epistemic work, through demands of epistemic adequacy and contestability, contrary to the claim that consensus conferences miss a window for epistemic opportunity (Solomon M, The social epistemology of NIH consensus conferences. In: Kincaid H, McKitrick J (ed) Establishing medical reality: methodological and metaphysical issues in philosophy of medicine. Springer, Dordrecht, 2007). Paying attention to the dynamics surrounding consensus, moreover, allows us to illustrate how the public understanding of science and the public use of the ideal of consensus could be well modified

The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Polymorphisms in the bovine HSP90AB1 gene are associated with heat tolerance in Thai indigenous cattle

Heat shock proteins act as molecular chaperones that have preferentially been transcribed in response to severe perturbations of the cellular homeostasis such as heat stress. Here the traits respiration rate (RR), rectal temperature (RT), pack cell volume (PCV) and the individual heat tolerance coefficient (HTC) were recorded as physiological responses on heat stress (environmental temperatures) in Bos taurus (crossbred Holstein Friesian; HF) and B. indicus (Thai native cattle: White Lamphun; WL and Mountain cattle; MT) animals (n = 47) in Thailand. Polymorphisms of the heat shock protein 90-kDa beta gene (HSP90AB1) were evaluated by comparative sequencing. Nine single nucleotide polymorphisms (SNP) were identified, i.e. three in exons 10 and 11, five in introns 8, 9, 10 and 11, and one in the 3′UTR. The exon 11 SNP g.5082C>T led to a missense mutation (alanine to valine). During the period of extreme heat (in the afternoon) RR and RT were elevated in each of the three breeds, whereas the PCV decreased. Mountain cattle and White Lamphun heifers recorded significantly better physiologic parameters (p < 0.05) in all traits considered, including or particularly HTC than Holstein Friesian heifers. The association analysis revealed that the T allele at SNP g.4338T>C within intron 3 improved the heat tolerance (p < 0.05). Allele T was exclusively found in White Lamphun animals and to 84% in Mountain cattle. Holstein Friesian heifers revealed an allele frequency of only 18%. Polymorphisms within HSP90AB1 were not causative for the physiological responses; however, we propose that they should at least be used as genetic markers to select appropriate breeds for hot climates

Forest chimpanzees (Pan troglodytes verus) remember the location of numerous fruit trees

It is assumed that spatial memory contributes crucially to animal cognition since animals’ habitats entail a large number of dispersed and unpredictable food sources. Spatial memory has been investigated under controlled conditions, with different species showing and different conditions leading to varying performance levels. However, the number of food sources investigated is very low compared to what exists under natural conditions, where food resources are so abundant that it is difficult to precisely identify what is available. By using a detailed botanical map containing over 12,499 trees known to be used by the Taï chimpanzees, we created virtual maps of all productive fruit trees to simulate potential strategies used by wild chimpanzees to reach resources without spatial memory. First, we simulated different assumptions concerning the chimpanzees’ preference for a particular tree species, and, second, we varied the detection field to control for the possible use of smell to detect fruiting trees. For all these assumptions, we compared simulated distance travelled, frequencies of trees visited, and revisit rates with what we actually observed in wild chimpanzees. Our results show that chimpanzees visit rare tree species more frequently, travel shorter distances to reach them, and revisit the same trees more often than if they had no spatial memory. In addition, we demonstrate that chimpanzees travel longer distances to reach resources where they will eat for longer periods of time, and revisit resources more frequently where they ate for a long period of time during their first visit. Therefore, this study shows that forest chimpanzees possess a precise spatial memory which allows them to remember the location of numerous resources and use this information to select the most attractive resources

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells

Gain and Loss of Phototrophic Genes Revealed by Comparison of Two Citromicrobium Bacterial Genomes

Proteobacteria are thought to have diverged from a phototrophic ancestor, according to the scattered distribution of phototrophy throughout the proteobacterial clade, and so the occurrence of numerous closely related phototrophic and chemotrophic microorganisms may be the result of the loss of genes for phototrophy. A widespread form of bacterial phototrophy is based on the photochemical reaction center, encoded by puf and puh operons that typically are in a ‘photosynthesis gene cluster’ (abbreviated as the PGC) with pigment biosynthesis genes. Comparison of two closely related Citromicrobial genomes (98.1% sequence identity of complete 16S rRNA genes), Citromicrobium sp. JL354, which contains two copies of reaction center genes, and Citromicrobium strain JLT1363, which is chemotrophic, revealed evidence for the loss of phototrophic genes. However, evidence of horizontal gene transfer was found in these two bacterial genomes. An incomplete PGC (pufLMC-puhCBA) in strain JL354 was located within an integrating conjugative element, which indicates a potential mechanism for the horizontal transfer of genes for phototrophy

Compensatory T Cell Responses in IRG-Deficient Mice Prevent Sustained Chlamydia trachomatis Infections

The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of bacterial sexually transmitted diseases in the United States. In women C. trachomatis can establish persistent genital infections that lead to pelvic inflammatory disease and sterility. In contrast to natural infections in humans, experimentally induced infections with C. trachomatis in mice are rapidly cleared. The cytokine interferon-γ (IFNγ) plays a critical role in the clearance of C. trachomatis infections in mice. Because IFNγ induces an antimicrobial defense system in mice but not in humans that is composed of a large family of Immunity Related GTPases (IRGs), we questioned whether mice deficient in IRG immunity would develop persistent infections with C. trachomatis as observed in human patients. We found that IRG-deficient Irgm1/m3(-/-) mice transiently develop high bacterial burden post intrauterine infection, but subsequently clear the infection more efficiently than wildtype mice. We show that the delayed but highly effective clearance of intrauterine C. trachomatis infections in Irgm1/m3(-/-) mice is dependent on an exacerbated CD4+ T cell response. These findings indicate that the absence of the predominant murine innate effector mechanism restricting C. trachomatis growth inside epithelial cells results in a compensatory adaptive immune response, which is at least in part driven by CD4+ T cells and prevents the establishment of a persistent infection in mice