56 research outputs found
A Genome Wide Association Scan of Bovine Tuberculosis Susceptibility in Holstein-Friesian Dairy Cattle
peer-reviewedBackground: Bovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although
many factors influence infection and progression of the disease, there is a host genetic component and dissection of this
may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of
infection presents a noisy signal for genomewide association study.
Methodology/Principal Findings: We calculated a composite phenotype of genetic merit for TB susceptibility based on
disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was
compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three
SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p,1025, peaking at position 59588069, p = 4.0261026) with
tuberculosis susceptibility.
Conclusions/Significance: A genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it
contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not
previously been investigated for its role in tuberculosis infection
Factors for short-term outcomes in patients with a minor stroke: results from China National Stroke Registry
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial
Background:
The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.
Methods:
PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.
Findings:
Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.
Interpretation:
Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial
BackgroundThe safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.MethodsPANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.FindingsBetween Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.InterpretationMolnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community
Molecular cloning of the cDNA encoding a stress-inducible protein phosphatase 1 (PP1) catalytic subunit from French bean (Phaseolus vulgaris L.)
The overwintering of Antarctic krill, Euphausia superba, from an ecophysiological perspective
A major aim of this review is to determine
which physiological functions are adopted by adults and
larvae to survive the winter season with low food supply
and their relative importance. A second aim is to clarify the
extent to which seasonal variation in larval and adult krill
physiology is mediated by environmental factors with a
strong seasonality, such as food supply or day light. Experimental
studies on adult krill have demonstrated that speciWc
physiological adaptations during autumn and winter,
such as reduced metabolic rates and feeding activity, are
not caused simply by the scarcity of food, as was previously
assumed. These adaptations appear to be inXuenced
by the local light regime. The physiological functions that
larval krill adopt during winter (reduced metabolism,
delayed development, lipid utilisation, and variable growth
rates) are, in contrast to the adults, under direct control by
the available food supply. During winter, the adults often
seem to have little association with sea ice (at least until
early spring). The larvae, however, feed within sea ice but
mainly on the grazers of the ice algal community rather
than on the algae themselves. In this respect, a miss-match
in timing of the occurrence of the last phytoplankton
blooms in autumn and the start of the sea ice formation, as
has been increasingly observed in the west Antarctic Peninsula
(WAP) region, will impact larval krill development
during winter in terms of food supply and consequently the
krill stock in this region
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