Modeling and mapping isotopic patterns in the Northwest Atlantic derived from loggerhead sea turtles

Stable isotope analysis can be used to infer geospatial linkages of highly migratory species. Identifying foraging grounds of marine organisms from their isotopic signatures is becoming de rigueur as it has been with terrestrial organisms. Sea turtles are being increasingly studied using a combination of satellite telemetry and stable isotope analysis; these studies along with those from other charismatic, highly vagile, and widely distributed species (e.g., tuna, billfish, sharks, dolphins, whales) have the potential to yield large datasets to develop methodologies to decipher migratory pathways in the marine realm. We collected tissue samples (epidermis and red blood cells) for carbon (delta C-13) and nitrogen (delta N-15) stable isotope analysis from 214 individual loggerheads (Caretta caretta) in the Northwest Atlantic Ocean (NWA). We used discriminant function analysis (DFA) to examine how well delta C-13 and delta N-15 classify loggerhead foraging areas. The DFA model was derived from isotopic signatures of 58 loggerheads equipped with satellite tags to identify foraging locations. We assessed model accuracy with the remaining 156 untracked loggerheads that were captured at their foraging locations. The DFA model correctly identified the foraging ground of 93.0% of individuals with a probability greater than 66.7%. The results of the external validation (1) confirm that assignment models based on tracked loggerheads in the NWA are robust and (2) provide the first independent evidence supporting the use of these models for migratory marine organisms. Additionally, we used these data to generate loggerhead-specific delta C-13 and delta N-15 isoscapes, the first for a predator in the Atlantic Ocean. We found a latitudinal trend of delta C-13 values with higher values in the southern region (20-25 degrees N) and a more complex pattern with delta N-15, with intermediate latitudes (30-35 degrees N) near large coastal estuaries having higher delta N-15-enrichment. These results indicate that this method with further refinement may provide a viable, more spatially-explicit option for identifying loggerhead foraging grounds

Autosub Long Range 1500: A continuous 2000 km field trial

Long Range Autonomous Underwater Vehicles (LRAUVs) offer the potential to monitor the ocean at higher spatial and temporal resolutions compared to conventional ship-based techniques. The multi-week to multi-month endurance of LRAUVs enables them to operate independently of a support vessel, creating novel opportunities for ocean observation. The National Oceanography Centre’s Autosub Long Range is one of a small number of vehicles designed for a multi-month endurance. The latest iteration, Autosub Long Range 1500 (ALR1500), is a 1500 m depth-rated LRAUV developed for ocean science in coastal and shelf seas or in the epipelagic and meteorologic regions of the ocean. This paper presents the design of the ALR1500 and results from a five week continuous deployment from Plymouth, UK, to the continental shelf break and back again, a distance of approximately 2000km which consumed half of the installed energy. The LRAUV was unaccompanied throughout the mission and operated continuously beyond visual line of sight

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents

Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide (10panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

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

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Marion Catherine Bagley Correspondence

Entries include a biographical review newspaper clipping and a lengthy philosophical hand written biograph

The impact of life stage and pigment source on the evolution of novel warning signal traits

Our understanding of how novel warning color traits evolve in natural populations is largely based on studies of reproductive stages and organisms with endogenously produced pigmentation. In these systems, genetic drift is often required for novel alleles to overcome strong purifying selection stemming from frequency-dependent predation and positive assortative mating. Here, we integrate data from field surveys, predation experiments, population genomics, and phenotypic correlations to explain the origin and maintenance of geographic variation in a diet-based larval pigmentation trait in the redheaded pine sawfly (Neodiprion lecontei), a pine-feeding hymenopteran. Although our experiments confirm that N. lecontei larvae are indeed aposematic—and therefore likely to experience frequency-dependent predation—our genomic data do not support a historical demographic scenario that would have facilitated the spread of an initially deleterious allele via drift. Additionally, significantly elevated differentiation at a known color locus suggests that geographic variation in larval color is currently maintained by selection. Together, these data suggest that the novel white morph likely spread via selection. However, white body color does not enhance aposematic displays, nor is it correlated with enhanced chemical defense or immune function. Instead, the derived white-bodied morph is disproportionately abundant on a pine species with a reduced carotenoid content relative to other pine hosts, suggesting that bottom-up selection via host plants may have driven divergence among populations. Overall, our results suggest that life stage and pigment source can have a substantial impact the evolution of novel warning signals, highlighting the need to investigate diverse aposematic taxa to develop a comprehensive understanding of color variation in nature.peerReviewe