Eliciting a predatory response in the eastern corn snake (Pantherophis guttatus) using live and inanimate sensory stimuli: implications for managing invasive populations

North America's Eastern corn snake (Pantherophis guttatus) has been introduced to several islands throughout the Caribbean and Australasia where it poses a significant threat to native wildlife. Invasive snake control programs often involve trapping with live bait, a practice that, as well as being costly and labour intensive, raises welfare and ethical concerns. This study assessed corn snake response to live and inanimate sensory stimuli in an attempt to inform possible future trapping of the species and the development of alternative trap lures. We exposed nine individuals to sensory cues in the form of odour, visual, vibration and combined stimuli and measured the response (rate of tongue-flick [RTF]). RTF was significantly higher in odour and combined cues treatments, and there was no significant difference in RTF between live and inanimate cues during odour treatments. Our findings suggest chemical cues are of primary importance in initiating predation and that an inanimate odour stimulus, absent of simultaneous visual and vibratory cues, is a potential low-cost alternative trap lure for the control of invasive corn snake populations

Behavioral differences following ingestion of large meals and consequences for management of a harmful invasive snake: A field experiment

Many snakes are uniquely adapted to ingest large prey at infrequent intervals. Digestion of large prey is metabolically and aerobically costly, and large prey boluses can impair snake locomotion, increasing vulnerability to predation. Cessation of foraging and use of refugia with microclimates facilitating digestion are expected to be strategies employed by free-ranging snakes to cope with the demands of digestion while minimizing risk of predation. However, empirical observations of such submergent behavior from field experiments are limited. The brown treesnake (Serpentes: Colubridae: Boiga irregularis) is a nocturnal, arboreal, colubrid snake that was accidentally introduced to the island of Guam, with ecologically and economically costly consequences. Because tools for brown treesnake damage prevention generally rely on snakes being visible or responding to lures or baits while foraging, cessation of foraging activities after feeding would complicate management. We sought to characterize differences in brown treesnake activity, movement, habitat use, and detectability following feeding of large meals (rodents 33% of the snake’s unfed body mass) via radio telemetry, trapping, and visual surveys. Compared to unfed snakes, snakes in the feeding treatment group showed drastic decreases in hourly and nightly activity rates, differences in refuge height and microhabitat type, and a marked decrease in detectability by trapping and visual surveys. Depression of activity lasted approximately 5–7 days, a period that corresponds to previous studies of brown treesnake digestion and cycles of detectability. Our results indicate that management strategies for invasive brown treesnakes need to account for cycles of unavailability and underscore the importance of preventing spread of brown treesnakes to new environments where large prey are abundant and periods of cryptic behavior are likely to be frequent. Characterization of postfeeding behavior changes provides a richer understanding of snake ecology and foraging models for species that consume large prey

Grounding Word Learning in Space

Humans and objects, and thus social interactions about objects, exist within space. Words direct listeners' attention to specific regions of space. Thus, a strong correspondence exists between where one looks, one's bodily orientation, and what one sees. This leads to further correspondence with what one remembers. Here, we present data suggesting that children use associations between space and objects and space and words to link words and objects—space binds labels to their referents. We tested this claim in four experiments, showing that the spatial consistency of where objects are presented affects children's word learning. Next, we demonstrate that a process model that grounds word learning in the known neural dynamics of spatial attention, spatial memory, and associative learning can capture the suite of results reported here. This model also predicts that space is special, a prediction supported in a fifth experiment that shows children do not use color as a cue to bind words and objects. In a final experiment, we ask whether spatial consistency affects word learning in naturalistic word learning contexts. Children of parents who spontaneously keep objects in a consistent spatial location during naming interactions learn words more effectively. Together, the model and data show that space is a powerful tool that can effectively ground word learning in social contexts

Competitive Interactions between Invasive Nile Tilapia and Native Fish: The Potential for Altered Trophic Exchange and Modification of Food Webs

Recent studies have highlighted both the positive and negative impacts of species invasions. Most of these studies have been conducted on either immobile invasive plants or sessile fauna found at the base of food webs. Fewer studies have examined the impacts of vagile invasive consumers on native competitors. This is an issue of some importance given the controlling influence that consumers have on lower order plants and animals. Here, we present results of laboratory experiments designed to assess the impacts of unintended aquaculture releases of the Nile tilapia (Oreochromis niloticus), in estuaries of the Gulf of Mexico, on the functionally similar redspotted sunfish (Lepomis miniatus). Laboratory choice tests showed that tilapia prefer the same structured habitat that native sunfish prefer. In subsequent interspecific competition experiments, agonistic tilapia displaced sunfish from their preferred structured habitats. When a piscivore (largemouth bass) was present in the tank with both species, the survival of sunfish decreased. Based on these findings, if left unchecked, we predict that the proliferation of tilapia (and perhaps other aggressive aquaculture fishes) will have important detrimental effects on the structure of native food webs in shallow, structured coastal habitats. While it is likely that the impacts of higher trophic level invasive competitors will vary among species, these results show that consequences of unintended releases of invasive higher order consumers can be important

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1:a multicentre, single-blind, randomised trial

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep–wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10–14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0–100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI −0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (−2·02, −4·02 to −0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. Funding: The European Union Seventh Framework Programme

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease