Numerical abundance and biomass reveal different temporal trends of functional diversity change in tropical fish assemblages

Funding: Fisheries Society of the British Isles; European Research Council (Grant Number(s): ERC AdG BioTIME 250189); The Leverhulme Trust (Grant Number(s): RPG-2019-402).Understanding how the biodiversity of freshwater fish assemblages changes over time is an important challenge. Until recently most emphasis has been on taxonomic diversity but it is now clear that measures of functional diversity can shed new light on the mechanisms that underpin this temporal change. Fish biologists use different currencies, such as numerical abundance and biomass, to measure the abundance of fish species. However, because they are not necessarily equivalent, these alternative currencies have the potential to reveal different insights into trends of functional diversity in natural assemblages. Here we asked how conclusions about temporal trends in functional diversity are influenced by the way in which the abundance of species has been quantified. To do this we computed two informative metrics, for each currency, for 16 freshwater fish assemblages in Trinidad's Northern Range that had been surveyed repeatedly over five years. We found that numerical abundance and biomass uncover different directional trends in these assemblages for each facet of functional diversity, and as such inform hypotheses about the ways in which these systems are being restructured. On the basis of these results we concluded that a combined approach, in which both currencies are employed, contributes to our understanding of the ecological processes that are involved in biodiversity change in freshwater fish assemblages.Publisher PDFPeer reviewe

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

From species to communities : the signature of recreational use on a tropical river ecosystem

This work was funded by an ERC grant (BIOTIME 250189). A. E. M. thanks the Royal Society and M. D. thanks the Scottish Funding Council (MASTS HR09011) for support.Disturbance can impact natural communities in multiple ways. However, there has been a tendency to focus on single indicators of change when examining the effects of disturbance. This is problematic as classical diversity measures, such as Shannon and Simpson indices, do not always detect the effects of disturbance. Here, we instead take a multilevel, hierarchical approach, looking for signatures of disturbance in the capacity and diversity of the community, and also in allocation and demography at the population level. Using recreational use as an example of disturbance, and the freshwater streams of Trinidad as a model ecosystem, we repeatedly sampled the fish communities and physical parameters of eight pairs of recreational and nonrecreational sites every 3 months over a 28-month period. We also chose the Trinidadian guppy (Poecilia reticulata) as the subject of our population-level analyses. Regression tree analysis, together with analysis of deviance, revealed that community capacity and community species richness were greater at sites with higher levels of recreational use. Interestingly, measures of community diversity that took into account the proportional abundance of each species were not significantly associated with recreational use. Neither did we find any direct association between recreational use and proportion of guppy biomass in the community. However, population-level differences were detected in the guppy: Sex ratio was significantly more male-biased at more disturbed sites. Our findings emphasize the importance of considering multiple levels when asking how disturbance impacts a community. We advocate the use of a multilevel approach when monitoring the effects of disturbance, and highlight gaps in our knowledge when it comes to interpreting these effects.Publisher PDFPeer reviewe

Numerical abundance and biomass reveal different temporal trends of functional diversity change in tropical fish assemblages

Understanding how the biodiversity of freshwater fish assemblages changes over time is an important challenge. Until recently most emphasis has been on taxonomic diversity but it is now clear that measures of functional diversity can shed new light on the mechanisms that underpin this temporal change. Fish biologists use different currencies, such as numerical abundance and biomass, to measure the abundance of fish species. However, because they are not necessarily equivalent, these alternative currencies have the potential to reveal different insights into trends of functional diversity in natural assemblages. Here we asked how conclusions about temporal trends in functional diversity are influenced by the way in which the abundance of species has been quantified. To do this we computed two informative metrics, for each currency, for 16 freshwater fish assemblages in Trinidad's Northern Range that had been surveyed repeatedly over five years. We found that numerical abundance and biomass uncover different directional trends in these assemblages for each facet of functional diversity, and as such inform hypotheses about the ways in which these systems are being restructured. On the basis of these results we concluded that a combined approach, in which both currencies are employed, contributes to our understanding of the ecological processes that are involved in biodiversity change in freshwater fish assemblages

From species to communities:the signature of recreational use on a tropical river ecosystem

Disturbance can impact natural communities in multiple ways. However, there has been a tendency to focus on single indicators of change when examining the effects of disturbance. This is problematic as classical diversity measures, such as Shannon and Simpson indices, do not always detect the effects of disturbance. Here, we instead take a multilevel, hierarchical approach, looking for signatures of disturbance in the capacity and diversity of the community, and also in allocation and demography at the population level. Using recreational use as an example of disturbance, and the freshwater streams of Trinidad as a model ecosystem, we repeatedly sampled the fish communities and physical parameters of eight pairs of recreational and nonrecreational sites every 3 months over a 28-month period. We also chose the Trinidadian guppy (Poecilia reticulata) as the subject of our population-level analyses. Regression tree analysis, together with analysis of deviance, revealed that community capacity and community species richness were greater at sites with higher levels of recreational use. Interestingly, measures of community diversity that took into account the proportional abundance of each species were not significantly associated with recreational use. Neither did we find any direct association between recreational use and proportion of guppy biomass in the community. However, population-level differences were detected in the guppy: Sex ratio was significantly more male-biased at more disturbed sites. Our findings emphasize the importance of considering multiple levels when asking how disturbance impacts a community. We advocate the use of a multilevel approach when monitoring the effects of disturbance, and highlight gaps in our knowledge when it comes to interpreting these effects

Individual variation in reproductive behaviour is linked to temporal heterogeneity in predation risk

Variation in predation risk is a major driver of ecological and evolutionary change, and, in turn, of geographical variation in behaviour. While predation risk is rarely constant in natural populations, the extent to which variation in predation risk shapes individual behaviour in wild populations remains unclear. Here, we investigated individual differences in reproductive behaviour in 16 Trinidadian guppy populations and related it to the observed variation in predator biomass each population experienced. Our results show that high heterogeneity in predator biomass is linked to individual behavioural diversification. Increased within-population heterogeneity in predator biomass is also associated with behavioural polymorphism. Some individuals adjust the frequency of consensual mating behaviour in response to differences in sex ratio context, while others display constantly at elevated frequencies. This pattern is analogous to a ‘live fast, die young’ pace-of-life syndrome. Notably, both high and low mean differences in predator biomass led to a homogenization of individual frequency of consensual mating displays. Overall, our results demonstrate that individual behavioural variation is associated with heterogeneity in predator biomass, but not necessarily with changes in mean values of predator biomass. We suggest that heterogeneity in predator biomass is an informative predictor of adaptive responses to changes in biotic conditions

Individual variation in reproductive behaviour is linked to temporal heterogeneity in predation risk

Variation in predation risk is a major driver of ecological and evolutionary change, and, in turn, of geographical variation in behaviour. While predation risk is rarely constant in natural populations, the extent to which variation in predation risk shapes individual behaviour in wild populations remains unclear. Here, we investigated individual differences in reproductive behaviour in 16 Trinidadian guppy populations and related it to the observed variation in predator biomass each population experienced. Our results show that high heterogeneity in predator biomass is linked to individual behavioural diversification. Increased within-population heterogeneity in predator biomass is also associated with behavioural polymorphism. Some individuals adjust the frequency of consensual mating behaviour in response to differences in sex ratio context, while others display constantly at elevated frequencies. This pattern is analogous to a ‘live fast, die young’ pace-of-life syndrome. Notably, both high and low mean differences in predator biomass led to a homogenization of individual frequency of consensual mating displays. Overall, our results demonstrate that individual behavioural variation is associated with heterogeneity in predator biomass, but not necessarily with changes in mean values of predator biomass. We suggest that heterogeneity in predator biomass is an informative predictor of adaptive responses to changes in biotic conditions.PostprintPeer reviewe