Dismissive incomprehension: a use of purported ignorance to undermine others

This paper analyses a particular social phenomenon whereby a speaker purports ignorance of the meaning of another speaker’s speech in order to undermine that other speaker: dismissive incomprehension. It develops a speech act theory of the phenomenon, and develops its distinctive, and sometimes problematic perlocutionary character. After taking a look at some of the issues surrounding the phenomenon, the paper compares it to more fully studied features of our social lives, including epistemic injustice and gaslighting. It ends with some thoughts on counteracting the problematic cases of dismissive incomprehension

Responsive anionophores with AND logic multi-stimuli activation

Artificial ion transport systems have emerged as an important class of compounds that promise applications in chemotherapeutics as anticancer agents or to treat channelopathies. Stimulus-responsive systems that offer spatiotemporally controlled activity for targeted applications remain rare. Here we utilize dynamic hydrogen bonding interactions of a 4,6-dihydroxy-isophthalamide core to generate a modular platform enabling access to stimuli-responsive ion transporters that can be activated in response to a wide variety of external stimuli, including light, redox, and enzymes, with excellent OFF-ON activation profiles. Alkylation of the two free hydroxyl groups with stimulus-responsive moieties locks the amide bonds through intramolecular hydrogen bonding and hence makes them unavailable for anion binding and transport. Triggering using a particular stimulus to cleave both cages reverses the hydrogen bonding arrangement, to generate a highly preorganized anion binding cavity for efficient transmembrane transport. Integration of two cages that are responsive to orthogonal stimuli enables multi-stimuli activation, where both stimuli are required to trigger transport in an AND logic process. Importantly, the strategy provides a facile method to post-functionalize the highly active transporter core with a variety of stimulus-responsive moieties for targeted activation with multiple triggers

Ion carrier modulated MRI contrast †

An ion-responsive MRI contrast agent based on a POPC liposomal scaffold is generated that displays a large amplitude relaxivity switch. Entrapment of MR active Gd-DOTA within cholesterol-doped, i.e., membrane rigidified, liposomes dampens the MR response through diminished water exchange across the lipid bilayer. Relaxivity is re-established by integration of ion carriers in the liposome membrane to mediate solvated ion flux

The Transit Light Curve Project. X. A Christmas Transit of HD 17156b

Photometry is presented of the Dec. 25, 2007 transit of HD 17156b, which has the longest orbital period and highest orbital eccentricity of all the known transiting exoplanets. New measurements of the stellar radial velocity are also presented. All the data are combined and integrated with stellar-evolutionary modeling to derive refined system parameters. The planet's mass and radius are found to be 3.212_{-0.082}^{+0.069} Jupiter masses and 1.023_{-0.055}^{+0.070} Jupiter radii. The corresponding stellar properties are 1.263_{-0.047}^{+0.035} solar masses and 1.446_{-0.067}^{+0.099} solar radii. The planet is smaller by 1 sigma than a theoretical solar-composition gas giant with the same mass and equilibrium temperature, a possible indication of heavy-element enrichment. The midtransit time is measured to within 1 min, and shows no deviation from a linear ephemeris (and therefore no evidence for orbital perturbations from other planets). We provide ephemerides for future transits and superior conjunctions. There is an 18% chance that the orbital plane is oriented close enough to edge-on for secondary eclipses to occur at superior conjunction. Observations of secondary eclipses would reveal the thermal emission spectrum of a planet that experiences unusually large tidal heating and insolation variations.Comment: To appear in ApJ [26 pages

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement

We thank Innovate UK Edge for providing funding to allow this research to be carried out.Background  Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype44 and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time dependent receiver operator curves. Results Using next generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1%53 for pre-operative and post-operative models respectively. Conclusions The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient’s genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient specific responses to different biomaterials.Publisher PDFPeer reviewe

Global estimates of pregnancies at risk of Plasmodium falciparum and Plasmodium vivax infection in 2020 and changes in risk patterns since 2000.

BACKGROUND: Women are at risk of severe adverse pregnancy outcomes attributable to Plasmodium spp. infection in malaria-endemic areas. Malaria control efforts since 2000 have aimed to reduce this burden of disease. METHODS: We used data from the Malaria Atlas Project and WorldPop to calculate global pregnancies at-risk of Plasmodium spp. infection. We categorised pregnancies as occurring in areas of stable and unstable P. falciparum and P. vivax transmission. We further stratified stable endemicity as hypo-endemic, meso-endemic, hyper-endemic, or holo-endemic, and estimated pregnancies at risk in 2000, 2005, 2010, 2015, 2017, and 2020. FINDINGS: In 2020, globally 120.4M pregnancies were at risk of P. falciparum, two-thirds (81.0M, 67.3%) were in areas of stable transmission; 85 2M pregnancies were at risk of P. vivax, 93.9% (80.0M) were in areas of stable transmission. An estimated 64.6M pregnancies were in areas with both P. falciparum and P. vivax transmission. The number of pregnancies at risk of each of P. falciparum and P. vivax worldwide decreased between 2000 and 2020, with the exception of sub-Saharan Africa, where the total number of pregnancies at risk of P. falciparum increased from 37 3M in 2000 to 52 4M in 2020. INTERPRETATION: Historic investments in malaria control have reduced the number of women at risk of malaria in pregnancy in all endemic regions except sub-Saharan Africa. Population growth in Africa has outpaced reductions in malaria prevalence. Interventions that reduce the risk of malaria in pregnancy are needed as much today as ever

Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair

The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing

The effect and control of malaria in pregnancy and lactating women in the Asia-Pacific region

Half of all pregnancies at risk of malaria worldwide occur in the Asia-Pacific region, where Plasmodium falciparum and Plasmodium vivax co-exist. Despite substantial reductions in transmission, malaria remains an important cause of adverse health outcomes for mothers and offspring, including pre-eclampsia. Malaria transmission is heterogeneous, and infections are commonly subpatent and asymptomatic. High-grade antimalarial resistance poses a formidable challenge to malaria control in pregnancy in the region. Intermittent preventive treatment in pregnancy reduces infection risk in meso-endemic New Guinea, whereas screen-and-treat strategies will require more sensitive point-of-care tests to control malaria in pregnancy. In the first trimester, artemether-lumefantrine is approved, and safety data are accumulating for other artemisinin-based combinations. Safety of novel antimalarials to treat artemisinin-resistant P falciparum during pregnancy, and of 8-aminoquinolines during lactation, needs to be established. A more systematic approach to the prevention of malaria in pregnancy in the Asia-Pacific is required

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie