Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced—ie, unresectable or metastatic—melanoma. This criterion, however, ...excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population.
We did a randomised, double-blind, placebo-controlled, phase 2 trial in 20 German academic medical centres. Eligible patients were aged 18–80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Key exclusion criteria included uveal or mucosal melanoma, previous therapy with checkpoint inhibitors, and any previous immunosuppressive therapy within the 30 days before study drug administration. Eligible patients were randomly assigned (1:1:1), using a central, interactive, online system, to the nivolumab plus ipilimumab group (1 mg/kg of intravenous nivolumab every 3 weeks plus 3 mg/kg of intravenous ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab every 2 weeks), nivolumab monotherapy group (3 mg/kg of intravenous nivolumab every 2 weeks plus ipilimumab-matching placebo during weeks 1–12), or double-matching placebo group. The primary endpoint was the recurrence-free survival in the intention-to-treat population. The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported. This study is registered with ClinicalTrials.gov, NCT02523313, and is ongoing.
Between Sept 2, 2015, and Nov 20, 2018, 167 patients were randomly assigned to receive nivolumab plus ipilimumab (n=56), nivolumab (n=59), or placebo (n=52). As of July 2, 2019, at a median follow-up of 28·4 months (IQR 17·7–36·8), median recurrence-free survival was not reached in the nivolumab plus ipilimumab group, whereas median recurrence-free survival was 12·4 months (95% CI 5·3–33·3) in the nivolumab group and 6·4 months (3·3–9·6) in the placebo group. The hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0·23 (97·5% CI 0·12–0·45; p<0·0001), and for the nivolumab group versus placebo group was 0·56 (0·33–0·94; p=0·011). In the nivolumab plus ipilimumab group, recurrence-free survival at 1 year was 75% (95% CI 61·0–84·9) and at 2 years was 70% (55·1–81·0); in the nivolumab group, 1-year recurrence-free survival was 52% (38·1–63·9) and at 2 years was 42% (28·6–54·5); and in the placebo group, this rate was 32% (19·8–45·3) at 1 year and 14% (5·9–25·7) at 2 years. Treatment-related grade 3–4 adverse events were reported in 71% (95% CI 57–82) of patients in the nivolumab plus ipilimumab group and in 27% (16–40) of those in the nivolumab group. Treatment-related adverse events of any grade led to treatment discontinuation in 34 (62%) of 55 patients in the nivolumab plus ipilimumab group and seven (13%) of 56 in the nivolumab group. Three deaths from adverse events were reported but were considered unrelated to the study treatment.
Adjuvant therapy with nivolumab alone or in combination with ipilimumab increased recurrence-free survival significantly compared with placebo in patients with stage IV melanoma with no evidence of disease. The rates of grade 3–4 treatment-related adverse events in both active treatment groups were higher than the rates reported in previous pivotal trials done in advanced melanoma with measurable disease.
Bristol-Myers Squibb.
Summary Background The IMMUNED trial previously showed significant improvements in recurrence-free survival for adjuvant nivolumab plus ipilimumab as well as for adjuvant nivolumab alone in patients ...with stage IV melanoma with no evidence of disease after resection or radiotherapy. Here, we report the final analysis, including overall survival data. Methods IMMUNED was an investigator-sponsored, double-blind, placebo-controlled, three-arm, phase 2 trial conducted in 20 academic medical centres in Germany. Eligible patients were aged 18–80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Patients were randomly assigned (1:1:1) to either nivolumab plus ipilimumab (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks), nivolumab monotherapy (nivolumab 3 mg/kg every 2 weeks), or matching placebo, for up to 1 year. The primary endpoint was recurrence-free survival in the intention-to-treat population. Secondary endpoints were time-to-recurrence, overall survival, progression-free survival or recurrence-free survival 2 (in patients in the placebo group who crossed over to nivolumab monotherapy after experiencing disease recurrence), and safety endpoints. This trial is registered on ClinicalTrials.gov (NCT02523313), and is complete. Findings Between Sept 2, 2015, and Nov 20, 2018, 175 patients were enrolled in the study, and 167 were randomly assigned to receive either nivolumab plus ipilimumab (n=56), nivolumab plus ipilimumab-matching placebo (n=59), or double placebo control (n=52). At a median follow-up of 49·2 months (IQR 34·9–58·1), 4-year recurrence-free survival was 64·2% (95% CI 49·2–75·9) in the nivolumab plus ipilimumab group, 31·4% (19·7–43·8) in the nivolumab alone group, and 15·0% (6·7–26·6) in the placebo group. The hazard ratio (HR) for recurrence for the nivolumab plus ipilimumab group versus placebo was 0·25 (97·5% CI 0·13–0·48; p<0·0001), and for the nivolumab group versus placebo was 0·60 (0·36–1·00; p=0·024). Median overall survival was not reached in any treatment group. The HR for overall survival was significantly in favour of the nivolumab plus ipilimumab group versus placebo (HR 0·41; 95% CI 0·17–0·99; p=0·040), but not for the nivolumab group versus placebo (HR 0·75; 0·36–1·56; p=0·44). 4-year overall survival was 83·8% (95% CI 68·8–91·9) in the nivolumab plus ipilimumab group, 72·6% (57·4–83·2) in the nivolumab alone group, and 63·1% (46·9–75·6) in the placebo group. The median progression-free survival or recurrence-free survival 2 of patients in the placebo group who crossed over to nivolumab monotherapy after experiencing disease recurrence was not reached (95% CI 21·2 months to not reached). Rates of grade 3–4 treatment-related adverse events remained largely unchanged compared with our previous report, occurring in 71% (95% CI 57–82) of the nivolumab plus ipilimumab group, and 29% (95% CI 17–42) of patients receiving nivolumab alone. There were no treatment-related deaths. Interpretation Both active regimens continued to show significantly improved recurrence-free survival compared with placebo in patients with stage IV melanoma with no evidence of disease who were at high risk of recurrence. Overall survival was significantly improved for patients receiving nivolumab plus ipilimumab compared with placebo. Use of subsequent anti-PD-1-based therapy was high in patients in the placebo group after recurrence and most likely impacted the overall survival comparison of nivolumab alone versus placebo. The recurrence-free and overall survival benefit of nivolumab plus ipilimumab over placebo reinforces the change of practice already initiated for the treatment of patients with stage IV melanoma with no evidence of disease. Funding Bristol-Myers Squibb.
Merkel cell carcinoma (MCC) is an immunogenic but aggressive skin cancer. Even after complete resection and radiation, relapse rates are high. PD-1 and PD-L1 checkpoint inhibitors showed clinical ...benefit in advanced MCC. We aimed to assess efficacy and safety of adjuvant immune checkpoint inhibition in completely resected MCC (ie, a setting without an established systemic standard-of-care treatment).
In this multicentre phase 2 trial, patients (any stage, Eastern Cooperative Oncology Group performance status 0–1) at 20 academic medical centres in Germany and the Netherlands with completely resected MCC lesions were randomly assigned 2:1 to receive nivolumab 480 mg every 4 weeks for 1 year, or observation, stratified by stage (American Joint Committee on Cancer stages 1–2 vs stages 3–4), age (<65 vs ≥65 years), and sex. Landmark disease-free survival (DFS) at 12 and 24 months was the primary endpoint, assessed in the intention-to-treat populations. Overall survival and safety were secondary endpoints. This planned interim analysis was triggered when the last-patient-in was followed up for more than 1 year. This study is registered with ClinicalTrials.gov (NCT02196961) and with the EU Clinical Trials Register (2013-000043-78).
Between Oct 1, 2014, and Aug 31, 2020, 179 patients were enrolled (116 65% stage 3–4, 122 68% ≥65 years, 111 62% male). Stratification factors (stage, age, sex) were balanced across the nivolumab (n=118) and internal control group (observation, n=61); adjuvant radiotherapy was more common in the control group. At a median follow-up of 24·3 months (IQR 19·2–33·4), median DFS was not reached (between-groups hazard ratio 0·58, 95% CI 0·30–1·12); DFS rates in the nivolumab group were 85% at 12 months and 84% at 24 months, and in the observation group were 77% at 12 months and 73% at 24 months. Overall survival results were not yet mature. Grade 3–4 adverse events occurred in 48 42% of 115 patients who received at least one dose of nivolumab and seven 11% of 61 patients in the observation group. No treatment-related deaths were reported.
Adjuvant therapy with nivolumab resulted in an absolute risk reduction of 9% (1-year DFS) and 10% (2-year DFS). The present interim analysis of ADMEC-O might suggest clinical use of nivolumab in this area of unmet medical need. However, overall survival events rates, with ten events in the active treatment group and six events in the half-the-size observation group, are not mature enough to draw conclusions. The explorative data of our trial support the continuation of ongoing, randomised trials in this area. ADMEC-O suggests that adjuvant immunotherapy is clinically feasible in this area of unmet medical need.
Bristol Myers Squibb.
Abstract Aims MMORPG addiction has been associated with self-concept impairments and increased identification with the own avatar. Yet, the underlying neurobiological mechanisms of ...self-identification with avatars, especially reflected in the left angular gyrus (AG), have only been assessed in regular gamers. Therefore, the study aims to examine neurobiological processes in addicted MMORPG players while evaluating their own and their personal avatar's body image (physical self-concept). Methods Sixteen addicted and seventeen non-addicted gamers underwent functional Magnetic Resonance Imaging (fMRI) while viewing images of themselves, their own avatar and unfamiliar persons. The Body Image Questionnaire (FKB-20) and Visual Analog Scales (VAS) assessing the degree of attractiveness, sympathy and gender identity of the self, of the avatar as well as of the unfamiliar persons were applied. Results Addicts showed a significantly extended negative body image and lower gender identity levels as well as decreased bilateral brain activations in the AG and the middle occipital gyrus during self-perception. They further exhibited higher activations in the left AG during avatar-perception. Regression analyses in the overall group and in addicted gamers indicated a significant positive correlation between gender identity and brain activation in the left AG during self-perception. Conclusions Our results confirm addicted MMORPG players to have physical self-concept deficits which may be related to hypoactivations in the AG. The findings further indicate addicted gamers to have a tendency to identify themselves easier with their own avatar than with their real self. Lower gender identity levels might be associated with physical self-concept deficits in MMORPG addiction.
Background
In late 2019, first cases of coronavirus disease 2019, or COVID‐19, caused by the novel coronavirus SARS‐CoV‐2, were reported in Wuhan, China. Subsequently COVID‐19 spread rapidly around ...the world. To contain the ensuing pandemic, numerous countries have implemented control measures related to international travel, including border closures, partial travel restrictions, entry or exit screening, and quarantine of travellers.
Objectives
To assess the effectiveness of travel‐related control measures during the COVID‐19 pandemic on infectious disease and screening‐related outcomes.
Search methods
We searched MEDLINE, Embase and COVID‐19‐specific databases, including the WHO Global Database on COVID‐19 Research, the Cochrane COVID‐19 Study Register, and the CDC COVID‐19 Research Database on 26 June 2020. We also conducted backward‐citation searches with existing reviews.
Selection criteria
We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across national borders during the COVID‐19 pandemic. We also included studies concerned with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as indirect evidence. Primary outcomes were cases avoided, cases detected and a shift in epidemic development due to the measures. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome.
Data collection and analysis
One review author screened titles and s; all excluded s were screened in duplicate. Two review authors independently screened full texts. One review author extracted data, assessed risk of bias and appraised study quality. At least one additional review author checked for correctness of all data reported in the 'Risk of bias' assessment, quality appraisal and data synthesis. For assessing the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, ROBINS‐I for observational ecological studies and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed certainty of evidence with GRADE, and the review author team discussed ratings.
Main results
We included 40 records reporting on 36 unique studies. We found 17 modelling studies, 7 observational screening studies and one observational ecological study on COVID‐19, four modelling and six observational studies on SARS, and one modelling study on SARS and MERS, covering a variety of settings and epidemic stages.
Most studies compared travel‐related control measures against a counterfactual scenario in which the intervention measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of travel restrictions, or a combination of measures.
There were concerns with the quality of many modelling studies and the risk of bias of observational studies. Many modelling studies used potentially inappropriate assumptions about the structure and input parameters of models, and failed to adequately assess uncertainty. Concerns with observational screening studies commonly related to the reference test and the flow of the screening process.
Studies on COVID‐19
Travel restrictions reducing cross‐border travel Eleven studies employed models to simulate a reduction in travel volume; one observational ecological study assessed travel restrictions in response to the COVID‐19 pandemic. Very low‐certainty evidence from modelling studies suggests that when implemented at the beginning of the outbreak, cross‐border travel restrictions may lead to a reduction in the number of new cases of between 26% to 90% (4 studies), the number of deaths (1 study), the time to outbreak of between 2 and 26 days (2 studies), the risk of outbreak of between 1% to 37% (2 studies), and the effective reproduction number (1 modelling and 1 observational ecological study). Low‐certainty evidence from modelling studies suggests a reduction in the number of imported or exported cases of between 70% to 81% (5 studies), and in the growth acceleration of epidemic progression (1 study).
Screening at borders with or without quarantine Evidence from three modelling studies of entry and exit symptom screening without quarantine suggests delays in the time to outbreak of between 1 to 183 days (very low‐certainty evidence) and a detection rate of infected travellers of between 10% to 53% (low‐certainty evidence).
Six observational studies of entry and exit screening were conducted in specific settings such as evacuation flights and cruise ship outbreaks. Screening approaches varied but followed a similar structure, involving symptom screening of all individuals at departure or upon arrival, followed by quarantine, and different procedures for observation and PCR testing over a period of at least 14 days. The proportion of cases detected ranged from 0% to 91% (depending on the screening approach), and the positive predictive value ranged from 0% to 100% (very low‐certainty evidence). The outcomes, however, should be interpreted in relation to both the screening approach used and the prevalence of infection among the travellers screened; for example, symptom‐based screening alone generally performed worse than a combination of symptom‐based and PCR screening with subsequent observation during quarantine.
Quarantine of travellers Evidence from one modelling study simulating a 14‐day quarantine suggests a reduction in the number of cases seeded by imported cases; larger reductions were seen with increasing levels of quarantine compliance ranging from 277 to 19 cases with rates of compliance modelled between 70% to 100% (very low‐certainty evidence).
Authors' conclusions
With much of the evidence deriving from modelling studies, notably for travel restrictions reducing cross‐border travel and quarantine of travellers, there is a lack of 'real‐life' evidence for many of these measures. The certainty of the evidence for most travel‐related control measures is very low and the true effects may be substantially different from those reported here. Nevertheless, some travel‐related control measures during the COVID‐19 pandemic may have a positive impact on infectious disease outcomes. Broadly, travel restrictions may limit the spread of disease across national borders. Entry and exit symptom screening measures on their own are not likely to be effective in detecting a meaningful proportion of cases to prevent seeding new cases within the protected region; combined with subsequent quarantine, observation and PCR testing, the effectiveness is likely to improve. There was insufficient evidence to draw firm conclusions about the effectiveness of travel‐related quarantine on its own. Some of the included studies suggest that effects are likely to depend on factors such as the stage of the epidemic, the interconnectedness of countries, local measures undertaken to contain community transmission, and the extent of implementation and adherence.
Background
In late 2019, the first cases of coronavirus disease 2019 (COVID‐19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures ...related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers.
Objectives
To assess the effectiveness of international travel‐related control measures during the COVID‐19 pandemic on infectious disease transmission and screening‐related outcomes.
Search methods
We searched MEDLINE, Embase and COVID‐19‐specific databases, including the Cochrane COVID‐19 Study Register and the WHO Global Database on COVID‐19 Research to 13 November 2020.
Selection criteria
We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across international borders during the COVID‐19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID‐19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome.
Data collection and analysis
Two review authors independently screened titles and s and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements.
Main results
Overall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission.
Most studies compared travel‐related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures.
Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects.
Below we outline the results for each intervention category by illustrating the findings from selected outcomes.
Travel restrictions reducing or stopping cross‐border travel (31 modelling studies)
The studies assessed cases avoided and shift in epidemic development. We found very low‐certainty evidence for a reduction in COVID‐19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect.
There was very low‐certainty evidence that cross‐border travel controls can slow the spread of COVID‐19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure.
Screening at borders (13 modelling studies; 13 observational studies)
Screening measures covered symptom/exposure‐based screening or test‐based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely.
For symptom/exposure‐based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate‐certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low‐certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low‐certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low‐certainty evidence), although all but one study observed this proportion to be less than 54%.
For test‐based screening, one modelling study provided very low‐certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low‐certainty evidence).
Quarantine (12 modelling studies)
The studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low‐ to low‐certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low‐certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance.
Quarantine and screening at borders (7 modelling studies; 4 observational studies)
The studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low‐ to low‐certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low‐certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine.
Authors' conclusions
With much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross‐border travel and quarantine of travellers, there is a lack of 'real‐world' evidence. The certainty of the evidence for most travel‐related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure‐based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure‐based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel‐related control measures from a societal perspective.
Psychometric studies suggest that observed self-concept deficits in addicted massively multiplayer online role-playing game (MMORPG) are compensated through the replacement of their ideal (i.e., how ...an individual would like to be) by their own avatar (i.e., graphical agent in the virtual world). Neurobiological studies indicate that increased identification with their own avatar in regular MMORPG gamers is possibly reflected by enhanced avatar-referential brain activation in the left angular gyrus (AG). However, the neurobiological correlates reflecting the relations of the avatar to addicted gamers' self and ideal are still unexplored. Therefore, we compare these relations between addicted and nonaddicted MMORPG gamers. A sample of n = 15 addicted and n = 17 nonaddicted players underwent functional MRI (fMRI) while completing a Giessen-Test (GT)-derived paradigm assessing self-, ideal-, and avatar-related self-concept domains. Neurobiological analyses included the comparisons avatar versus self, avatar versus ideal, and avatar versus self, ideal. Psychometrically, addicts showed significantly lower scores on the self-concept subscale of 'social resonance,' that is, social popularity. In all avatar-related contrasts, within-group comparisons showed addicted players to exhibit significantly higher brain activations in the left AG. The between-groups comparisons revealed avatar-related left AG hyperactivations in addicts. Our results may suggest that addicted MMORPG players identify significantly more with their avatar than nonaddicted gamers. The concrete avatar might increasingly replace the rather abstract ideal in the transition from normal- controlled to addictive-compulsive MMORPG usage.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether ...increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen.
Meiofauna play an essential role in the diet of small and juvenile fish. However, it is less well documented which meiofaunal prey groups in the sediment are eaten by fish. Trophic relationships ...between five demersal fish species (solenette, goby, scaldfish, dab <20 cm and plaice <20 cm) and meiofaunal prey were investigated by means of comparing sediment samples and fish stomach contents collected seasonally between January 2009 and January 2010 in the German Bight. In all seasons, meiofauna in the sediment was numerically dominated by nematodes, whereas harpacticoids dominated in terms of occurrence and biomass. Between autumn and spring, the harpacticoid community was characterized by Pseudobradya minor and Halectinosoma canaliculatum, and in summer by Longipedia coronata. Meiofaunal prey dominated the diets of solenette and gobies in all seasons, occurred only seasonally in the diet of scaldfish and dab, and was completely absent in the diet of plaice. For all fish species (excluding plaice) and in each season, harpacticoids were the most important meiofauna prey group in terms of occurrence, abundance and biomass. High values of Ivlev’s index of selectivity for Pseudobradya spp. in winter and Longipedia spp. in summer provided evidence that predation on harpacticoids was species-selective, even though both harpacticoids co-occurred in high densities in the sediments. Most surficial feeding strategies of the studied fish species and emergent behaviours of Pseudobradya spp. and Longipedia spp. might have caused this prey selection. With increasing fish sizes, harpacticoid prey densities decreased in the fish stomachs, indicating a diet change towards larger benthic prey during the ontogeny of all fish species investigated.
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