Terrestrial emigration behaviour of two invasive crayfish species

To disperse between isolated waterbodies, freshwater organisms must often cross terrestrial barriers and many freshwater animals that are incapable of flight must rely on transport via flooding events, other animals or anthropogenic activity. Decapods such as crayfish, on the other hand, can disperse to nearby waterbodies by walking on land, a behaviour that has facilitated the spread of invasive species. Overland movement could play a key role in the management of non-native crayfish, though to what extent terrestrial emigration occurs in different species is poorly understood. Here, we directly compared the terrestrial emigration tendency of two non-native crayfish species in Great Britain; red swamp (Procambarus clarkii) and signal (Pacifastacus leniusculus) crayfish. We found that both species emigrated from the water and that there was no significant difference in terms of their terrestrial emigration tendency, suggesting that there is a risk both of these species will migrate overland and disperse to new habitats. This study shows that terrestrial emigration is an important behavioural trait to consider when preventing the escape of crayfish from aquaculture and further spread of invasive species

Closely related Lak megaphages replicate in the microbiomes of diverse animals.

Lak phages with alternatively coded ∼540 kbp genomes were recently reported to replicate in Prevotella in microbiomes of humans that consume a non-Western diet, baboons, and pigs. Here, we explore Lak phage diversity and broader distribution using diagnostic polymerase chain reaction and genome-resolved metagenomics. Lak phages were detected in 13 animal types, including reptiles, and are particularly prevalent in pigs. Tracking Lak through the pig gastrointestinal tract revealed significant enrichment in the hindgut compared to the foregut. We reconstructed 34 new Lak genomes, including six curated complete genomes, all of which are alternatively coded. An anomalously large (∼660 kbp) complete genome reconstructed for the most deeply branched Lak from a horse microbiome is also alternatively coded. From the Lak genomes, we identified proteins associated with specific animal species; notably, most have no functional predictions. The presence of closely related Lak phages in diverse animals indicates facile distribution coupled to host-specific adaptation

The Development of Videoconference-Based Support for People Living With Rare Dementias and Their Carers: Protocol for a 3-Phase Support Group Evaluation

BACKGROUND: People living with rarer dementias face considerable difficulty accessing tailored information, advice, and peer and professional support. Web-based meeting platforms offer a critical opportunity to connect with others through shared lived experiences, even if they are geographically dispersed, particularly during the COVID-19 pandemic. OBJECTIVE: We aim to develop facilitated videoconferencing support groups (VSGs) tailored to people living with or caring for someone with familial or sporadic frontotemporal dementia or young-onset Alzheimer disease, primary progressive aphasia, posterior cortical atrophy, or Lewy body dementia. This paper describes the development, coproduction, field testing, and evaluation plan for these groups. METHODS: We describe a 3-phase approach to development. First, information and knowledge were gathered as part of a coproduction process with members of the Rare Dementia Support service. This information, together with literature searches and consultation with experts by experience, clinicians, and academics, shaped the design of the VSGs and session themes. Second, field testing involved 154 Rare Dementia Support members (people living with dementia and carers) participating in 2 rounds of facilitated sessions across 7 themes (health and social care professionals, advance care planning, independence and identity, grief and loss, empowering your identity, couples, and hope and dementia). Third, a detailed evaluation plan for future rounds of VSGs was developed. RESULTS: The development of the small groups program yielded content and structure for 9 themed VSGs (the 7 piloted themes plus a later stages program and creativity club for implementation in rounds 3 and beyond) to be delivered over 4 to 8 sessions. The evaluation plan incorporated a range of quantitative (attendance, demographics, and geography; pre-post well-being ratings and surveys; psycholinguistic analysis of conversation; facial emotion recognition; facilitator ratings; and economic analysis of program delivery) and qualitative (content and thematic analysis) approaches. Pilot data from round 2 groups on the pre-post 3-word surveys indicated an increase in the emotional valence of words selected after the sessions. CONCLUSIONS: The involvement of people with lived experience of a rare dementia was critical to the design, development, and delivery of the small virtual support group program, and evaluation of this program will yield convergent data about the impact of tailored support delivered to geographically dispersed communities. This is the first study to design and plan an evaluation of VSGs specifically for people affected by rare dementias, including both people living with a rare dementia and their carers, and the outcome of the evaluation will be hugely beneficial in shaping specific and targeted support, which is often lacking in this population

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

The neurochemistry and morphology of functionally identified corneal polymodal nociceptors and cold thermoreceptors

<div><p>It is generally believed that the unencapsulated sensory nerve terminals of modality specific C- and Aδ-neurons lack structural specialization. Here we determined the morphology of functionally defined polymodal receptors and cold thermoreceptors in the guinea pig corneal epithelium. Polymodal receptors and cold thermoreceptors were identified by extracellular recording at the surface of the corneal epithelium. After marking the recording sites, corneas were processed to reveal immunoreactivity for the transient receptor potential channels TRPV1 (transient receptor potential cation channel, subfamily V, member 1) or TPRM8 (transient receptor potential cation channel subfamily M member 8). Polymodal receptor nerve terminals (n = 6) were TRPV1-immunoreactive and derived from an axon that ascended from the sub-basal plexus to the squamous cell layer where it branched into fibers that ran parallel to the corneal surface and terminated with small bulbar endings (ramifying endings). Cold thermoreceptor nerve terminals were TRPM8-immunoreactive (n = 6) and originated from an axon that branched as it ascended through the wing cell and squamous cell layers and terminated with large bulbar endings (complex endings). These findings indicate that modality specific corneal sensory neurons with unencapsulated nerve endings have distinct nerve terminal morphologies that are likely to relate to their function.</p></div

Immuno-labeling for TRPV1 at the polymodal receptor recording site where the electrical activity shown in Fig 4 was recorded.

<p>A, bright-field image showing within the white dotted circle the mark left on the corneal surface by the rim of the recording electrode. B, all axons in the field of view were revealed by β-tubulin III-IR (green). C, a TRPV1-IR (red) nerve terminal was located at the recording site. In B and C, the dotted circle approximates the dimensions of the electrode tip at the recording site revealed in A. The scale bar in A–C = 50 μm. D and E, show a 3-dimensional reconstruction of the TRPV1-IR nerve terminal from front (D) and side (E) views. The dashed lines in E approximate the boundaries of the corneal epithelium. The indentation of the epithelium was produced by the recording electrode.</p

The electrical activity recorded from a cold thermoreceptor nerve terminal at the corneal surface.

<p><b>A</b> and <b>B</b>, show the temperature of the solution superfusing the cornea (<b>A</b>) and the frequency of nerve terminal impulse (NTI) discharge (<b>B</b>). During heating and cooling the frequency of NTIs was decreased and increased, respectively. <b>C</b>, overlaid traces recorded during stimulation of the ciliary nerves with a train of 25 pulses at 1 Hz. At this recording site electrical stimulation evoked a single stimulus locked NTI. The insets in <b>C</b> show averages of the electrically evoked and spontaneous NTIs. The smaller amplitude of the spontaneous NTIs indicates they are likely to be initiated very close to site of recording (see [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195108#pone.0195108.ref025" target="_blank">25</a>]). In <b>C</b>, the stimulus artifact (SA) is indicated and during the flat line immediately following the SA the signal was out of the analogue-to-digital recording range.</p

The electrical activity recorded from a capsaicin-sensitive nerve terminal at the corneal surface.

<p>A, the frequency of NTI discharge before and during application of capsaicin (0.5 μM). In this receptor, there was a low level of ongoing NTI activity that was markedly increased by capsaicin. B, overlaid traces recorded during stimulation of the ciliary nerves with a train of 25 pulses at 1 Hz. At this recording site electrical stimulation evoked a single stimulus locked NTI. In B, the stimulus artifact (SA) is indicated and during the flat line immediately following the SA the signal was out of the analogue-to-digital recording range.</p

Immuno-labeling for TRPM8 at the cold thermoreceptor recording site where the electrical activity shown in Fig 1 was recorded.

<p>A, fluoro-gold fluorescence within the white dotted circle identifies the approximate location of the recording site. B, bright-field image showing within the white dotted circle the mark left on the corneal surface by the rim of the recording electrode. C, all axons in the field of view were revealed by β-tubulin III-IR (green). D, a TRPM8-IR (red) nerve terminal was located at the recording site. In C and D, the white dotted circle approximates dimensions of the electrode tip at the recording site revealed in B. The scale bar in A–D = 50 μm. E and F, show a 3-dimensional reconstruction of the TRPM8-IR nerve terminal viewed from the front (E) and side (F). Panel F shows an orthogonal projection of the image shown in D. In C–F, the asterisk marks the site where the parent axon of the TRPM8-IR nerve terminal enters into the epithelium through Bowman’s membrane. The dashed lines in F approximate the area occupied by the corneal epithelium.</p