Immature Survival Research Articles

Modelling approaches for histology-independent cancer drugs to inform NICE appraisals: a systematic review and decision-framework.

The first histology-independent marketing authorisation in Europe was granted in 2019. This was the first time that a cancer treatment was approved based on a common biomarker rather than the location in the body at which the tumour originated. This research aims to explore the implications for National Institute for Health and Care Excellence appraisals. Targeted reviews were undertaken to determine the type of evidence that is likely to be available at the point of marketing authorisation and the analyses required to support National Institute for Health and Care Excellence appraisals. Several challenges were identified concerning the design and conduct of trials for histology-independent products, the greater levels of heterogeneity within the licensed population and the use of surrogate end points. We identified approaches to address these challenges by reviewing key statistical literature that focuses on the design and analysis of histology-independent trials and by undertaking a systematic review to evaluate the use of response end points as surrogate outcomes for survival end points. We developed a decision framework to help to inform approval and research policies for histology-independent products. The framework explored the uncertainties and risks associated with different approval policies, including the role of further data collection, pricing schemes and stratified decision-making. We found that the potential for heterogeneity in treatment effects, across tumour types or other characteristics, is likely to be a central issue for National Institute for Health and Care Excellence appraisals. Bayesian hierarchical methods may serve as a useful vehicle to assess the level of heterogeneity across tumours and to estimate the pooled treatment effects for each tumour, which can inform whether or not the assumption of homogeneity is reasonable. Our review suggests that response end points may not be reliable surrogates for survival end points. However, a surrogate-based modelling approach, which captures all relevant uncertainty, may be preferable to the use of immature survival data. Several additional sources of heterogeneity were identified as presenting potential challenges to National Institute for Health and Care Excellence appraisal, including the cost of testing, baseline risk, quality of life and routine management costs. We concluded that a range of alternative approaches will be required to address different sources of heterogeneity to support National Institute for Health and Care Excellence appraisals. An exemplar case study was developed to illustrate the nature of the assessments that may be required. Adequately designed and analysed basket studies that assess the homogeneity of outcomes and allow borrowing of information across baskets, where appropriate, are recommended. Where there is evidence of heterogeneity in treatment effects and estimates of cost-effectiveness, consideration should be given to optimised recommendations. Routine presentation of the scale of the consequences of heterogeneity and decision uncertainty may provide an important additional approach to the assessments specified in the current National Institute for Health and Care Excellence methods guide. Further exploration of Bayesian hierarchical methods could help to inform decision-makers on whether or not there is sufficient evidence of homogeneity to support pooled analyses. Further research is also required to determine the appropriate basis for apportioning genomic testing costs where there are multiple targets and to address the challenges of uncontrolled Phase II studies, including the role and use of surrogate end points. This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 76. See the NIHR Journals Library website for further project information.

Parametric Survival Extrapolation of Early Survival Data in Economic Analyses: A Comparison of Projected Versus Observed Updated Survival

ObjectivesTo establish the value of cancer drugs by cost-effectiveness analysis, lifetime parametric survival extrapolations are often fitted to early data. Recent literature suggests that the benefit of cancer agents in primary publications is often different compared with updated data. This study aimed to examine the projected survival based on parametric extrapolations compared with observed survival based on updated data. MethodsUS Food and Drug Administration oncology approvals from January 2006 to December 2015 were reviewed to identify randomized controlled trials, with updated overall survival (OS) or progression-free survival (PFS) data within 5 years. Individual patient data were reconstructed using established methods on initial and updated publications. Projected survival was calculated as the best-fit parametric restricted mean survival time (RMST) based on extrapolated initial Kaplan-Meier curves whereas observed survival was calculated as observed RMST based on updated Kaplan-Meier curves. Mean deviations, mean absolute error (MAE), mean absolute percentage error, and linear regressions were conducted to examine the relationship between projected and observed survival. ResultsIn total, 32 randomized controlled trials were included. The MAE between the projected RMST and observed RMST was 3.18 months (OS) and 2.84 months (PFS) and absolute percentage error of 100% (OS) and 23% (PFS), suggesting substantial imprecision of the projected RMST in predicting the updated RMST. The linear regression indicated MAE increased as time extrapolated and as the percentage of censored patients increased. ConclusionsThis study demonstrated substantial difference in projected survival between initial and updated publications. Health technology assessment committees need to be aware of the potential uncertainty of incremental effectiveness and resultant value-for-money assessment when making reimbursement decisions based on initial publications with immature survival data.

Helicoverpa armigera and Helicoverpa zea hybridization: constraints, heterosis, and implications for pest management.

The invasion of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) into the New World has made it possible for this pest to hybridize with a native American species, H. zea (Boddie), under natural conditions. We investigated the viability and development of hybrids of these two Helicoverpa species. We reared the parental species and evaluated crosses between H. armigera males and H. zea females and vice versa, two intercrosses between hybrids, and eight backcrosses between hybrids and parental species. We estimated the length of immature stages, fecundity, survival, sex ratio, and heterosis. Although hybridization occcurred, with heterosis during the development of immatures, reproductive incompatibilities also were observed between the parental species and between hybrids from subsequent crosses. The interspecific crosses between hybrids and backcrosses confirmed the possibility of introgression events and their perpetuation in field populations. The results indicate that hybridization events are favored at high population levels, while at low population levels the 'species identities' will be maintained. The possibility of interspecific gene flow and its perpetuation through successive crosses and backcrosses suggests several recommenations for management. Populations of both species should be maintained at an equilibrium level to reduce the chance of interspecific crosses, which are presumably more likely to occur during pest outbreaks. The existence of hybridization and resistance to different active pesticide ingredients should be monitored. All practices related to managing the resistance of these pests to chemical and biological insecticides should be systematized to reduce the chance of selecting for resistant individuals.

Density-dependent winter survival of immatures in an irruptive raptor with pulsed breeding.

Highly mobile predators can show strong numerical responses to pulsed resources, sometimes resulting in irruptions where large numbers of young invade landscapes at a continental scale. High production of young in irruption years may have a strong influence on the population dynamics unless immature survival is reduced compared to non-irruption years. This could occur if subordinate individuals (mainly immatures) are forced into suboptimal habitats due to density-dependent effects in irruption years. To test whether irruptive individuals had lower survival than non-irruptive ones, we combined necropsy results (N = 365) with telemetry (N = 185) from more than 20years to record timing and causes of mortality in snowy owls (Bubo scandiacus), which irrupt into eastern North America during winter following high breeding output caused by lemming peaks in the Arctic. Mortality was more than four times higher in irruption years than non-irruption years, but only for immatures, and occurred disproportionately in early winter for immatures, but not adults. Mortality was also higher in eastern North America, where owl abundance fluctuates considerably between years, compared to core winter regions of the Arctic and Prairies where populations are more stable. Most mortality was not due to starvation, but rather associated with human activity, especially vehicle collisions. We conclude that immature snowy owls that irrupt into eastern North America are limited by density-dependent factors, such as increased competition forcing individuals to occupy risky human-altered habitats. For highly mobile, irruptive animals, resource pulses may have a limited impact on population dynamics due to low subsequent survival of breeding output during the nonbreeding season.

P48.05 Is Relapse-Free Survival at 2-Years an Appropriate Surrogate for Overall Survival at 5-Years in EGFR-mutated Resected NSCLC?

The phase 3 ADAURA trial identified a highly significant hazard ratio (HR) of 0.17 for disease-free (i.e., relapse-free) survival (RFS) favoring adjuvant osimertinib, but a non-significant immature overall survival (OS) HR of 0.40. However, is RFS an appropriate surrogate for OS in this setting? OS is still the gold standard in health technology assessments, but it will take years for ADAURA’s OS data to mature. In the ADAURA-eligible setting, we compared HRs for clinico-demographic-treatment variables between RFS censored at 2 years (RFS-2YRS) with OS censored at 5 years (OS-5YRS), and explored reasons why such a relationship may exist. A retrospective analysis from Princess Margaret Cancer Centre of all patients with EGFR-mutated resected NSCLC (diagnosed 2012-2018) utilized Kaplan-Meier curves and Cox regression to compare RFS-2YRS and OS-5YRS for common clinico-demographic-treatment variables. We explored how these patients were managed after relapse, and compared their OS outcomes to patients with de novo advanced/metastatic EGFR-mutated disease. Among 104 patients with EGFR-mutated resected NSCLC, female=66%; median age=67 years; never-smokers=73%; Stage IB=41%; Stage II=34%; Stage IIIA=25%. Univariable Cox regression results comparing RFS-2YRS and OS-5YRS are presented in the table. Overall, HRs were either similar or slightly attenuated at OS-5YRs when compared to RFS-2YRS. Among the n=63 (61%) patients who relapsed, 81% were due to distant metastases. Only 8% were treated with curative surgery or chemoradiation at the time of relapse (an additional 3% were offered but declined curative treatment). The remaining patients (92%) were managed as advanced/incurable cancer. Of those treated at Princess Margaret, 75% received first-line EGFR-TKI therapy, while 4% received other systemic therapies; 8% had developed multifocal disease that was monitored rather than treated systemically; and 8% died before systemic therapy could be started or had concurrent comorbid conditions. Starting with diagnosis of advanced/metastatic disease, there were no differences in the OS of this relapsed cohort (n=63) versus 252 de novo advanced/metastatic NSCLC (log-rank p=0.29). The adjusted HR for OS was 0.82 (95% CI: 0.55-1.24 ). Among early-stage patients with EGFR-mutated resected NSCLC, 92% were treated as advanced/metastatic disease at the time of relapse. Their survival (from the time of relapse) was similar to those diagnosed initially with EGFR-mutated advanced/metastatic cancer. This information helps explain why relapse-free survival censored at 2-years represents an acceptable surrogate endpoint for overall survival at 5-years.

Evaluation of Advanced Therapy Medicinal Products by the National Institute for Health and Care Excellence (NICE): An Updated Review

This review discusses the methodological challenges to the evaluation of advanced therapy medicinal products (ATMPs) by the UK National Institute for Health and Care Excellence (NICE). We analysed the health technology appraisals (both published and in development) of ATMPs conducted by NICE in England until July 2021. A total of 14 health technology appraisals of ATMPs were included, of which two were in development and 12 had been published. There were ten gene therapy products (talimogene laherparepvec [TA410], strimvelis [HST7], tisagenlecleucel [TA554 and TA567], axicabtagene ciloleucel [TA559], voretigene neparvovec [HST11], autologous anti-CD19-transduced CD3+ cells [TA677], betibeglogene autotemcel [ID968], onasemnogene abeparvovec [HST15] and OTL-200 [ID1666]), one tissue engineered product (holoclar [TA467]) and three somatic cell therapy products (darvadstrocel [TA556] and autologous chondrocyte implantation [ACI] [TA477 and TA508]). Only three of these technologies were not recommended by NICE, although four were only recommended within the Cancer Drugs Fund. There was large uncertainty in the assessment of clinical effectiveness, as evidence relied mostly on small, single-arm, open-label studies. There were also several concerns in the cost-effectiveness evaluations, such as limited information on health-related quality of life, immature survival data due to short follow-up, and unclear curative potential. Substantial risk may be incurred with ATMPs, which have high upfront and possibly irrecoverable costs but uncertain long-term benefits. In conclusion, the challenges raised by the economic appraisal of ATMPs, albeit not unique, may be exacerbated by the uncertainty related to the often scant evidence base. Adaptations of the conventional decision-making process rather than completely new methods may improve appraisals of ATMPs.

The real-world efficacy and safety of anlotinib in advanced non-small cell lung cancer

PurposeAnlotinib is an anti-angiogenetic multi-targeted tyrosine kinase inhibitor. This study aimed to evaluate the efficacy and safety of anlotinib in advanced non-small cell lung cancer (aNSCLC) in the real world.MethodsPatients with aNSCLC receiving anlotinib were enrolled in two cohorts (treatment naive and previously treated). The endpoints included progression-free survival (PFS), overall survival (OS) and anlotinib-related adverse events (ar-AEs).Results203 patients accrued in the study. In the treatment-naïve cohort (n = 80), the PFS was 7.4 (95% confidence interval [CI] 4.1–10.7) and OS was 10.8 (95% CI 5.8–15.8) months of monotherapy group (immature survival for combination group). In previously treated cohort (n = 123), the PFS was 8.0 months (95% CI 6.1–9.9) in the combination group and 4.3 months (95% CI 2.1–6.6) in the monotherapy group (hazard ratio [HR] 0.49; 95% CI 0.29–0.83; p = 0.007), respectively. The OS was 18.5 months (95% CI 10.5–26.6) in the combination group and 7.8 months (95% CI 7.1–8.4) in the monotherapy group (HR 0.38; 95% CI 0.22–0.66; p = 0.001), respectively. The ar-AEs of grade ≥ 3 in the monotherapy and the combination groups were hypertension (9.0 and 8.7%), fatigue (8.1 and 7.6%), hand-foot syndrome (8.1 and 6.5%), diarrhea (5.4 and 8.7%), proteinuria (5.4 and 5.4%), and mucositis oral (6.3 and 8.7%).ConclusionIn aNSCLC, anlotinib monotherapy has a promising efficacy in the first-line setting. It may be an option for those who are ineligible for chemotherapy; anlotinib combination therapy in a ≥ second-line setting showed manageable toxicities and encouraging efficacy, indicating a good application prospect.Trial registrationThis study was retrospectively registered with ISRCTN Registry (ID ISRCTN35543977) on January 26th, 2021 and Chinese Clinical Trial Register (ChiCTR2000032265) on April 4th, 2020.Supplementary informationThe online version contains supplementary material available at 10.1007/s00432-021-03752-x.

Temperature-dependent phenology of the parasitoid Fopius arisanus on the host Bactrocera dorsalis.

Fopius arisanus (Sonan), an egg-pupal parasitoid of numerous fruit fly species, was recently introduced into Africa for the control of the Oriental fruit fly, Bactrocera dorsalis (Hendel). In this study, life-table data of F. arisanus were generated under laboratory conditions at six constant temperatures (15, 20, 25, 30, 28 and 35°C; 75% RH, L12:D12 photoperiod) and under variable conditions in a screenhouse on B. dorsalis. Several non-linear functions were fitted to model species development, mortality, longevity and oviposition using the Insect Life Cycle Modeling (ILCYM) software. The established phenology models were stochastically simulated at variable temperatures to estimate the life table parameters. Fopius arisanus completed development from egg to adult at all the temperatures tested except at 35°C. Mean developmental time from egg to adult was inversely proportional to the temperature. The minimum temperature threshold (Tmin) from egg to adult was 8.15°C, while the maximum temperature threshold (Tmax) was estimated at 34.2°C. The optimal temperature for immature stages survival was predicted for 20-30°C. The optimum fecundity estimated was 251 eggs/female at 22°C. Following the stochastic simulations under natural conditions of the selected agro-ecological zones, it appears that the Humid Forest with Bimodal Rainfall provides a suitable thermal condition for potential population growth of F. arisanus. The present study shows the importance of temperature on the demographic parameters of F. arisanus. Implications of present findings on the biological control of B. dorsalis under climate change scenarios is discussed.

Mechanisms driving component Allee effects during invasions: using a biological control agent as model invader

1. A demographic Allee effect refers to increasing per capita population growth with increasing abundance. It arises from component Allee effects, which exist when some component of individual fitness has a positive relationship with density. Newly arrived populations tend to be small, and their establishment success is influenced by various factors, including demographic Allee effects. Identifying mechanisms driving the Allee effect is of relevance for understanding establishment failure, developing strategies for improving biological control and conservation, and for managing biological invasions.2. We utilised an invasive plant biocontrol agent, Neolema ogloblini, as model to study Allee effects experienced by invading populations. We investigated mating failure and predator satiation as two component Allee effects that could potentially drive a demographic Allee effect in N. ogloblini populations.3. We released unmated adults onto isolated host patches using five release sizes and evaluated the mating status of females after 3 weeks in the field. The probability of being mated increased as number of males recovered increased, suggesting the presence of a mating‐failure component Allee effect in very small populations of N. ogloblini. Exclosures were used to evaluate survival of immatures of N. ogloblini developing in small group sizes, either in the presence or absence of generalist predators. Results revealed high levels of predation, but a positive relationship between larval survival and group size in the presence of generalist predators could not be verified.4. Our study identified relevant life‐history traits contributing to establishment failure in N. ogloblini and demonstrates the value of biocontrol agents as models to study mechanisms of species invasion.

PCN134 Assessing the Relationship between Immature and Mature Overall Survival (OS) Outcomes on HTA Decision-Making: A Study of UK Nice Decisions and the Case for Coverage with Evidence Development

To understand how magnitude of effect and early readout of OS outcomes can be used to inform conditional coverage decisions with continued evidence development. Analysis of NICE oncology appraisals published between 2011-2017 which initially presented immature interim OS results (<50% maturity) and for which subsequent OS results have been published. Analysis based on mean OS could not be performed due to Kaplan Meier and extrapolation data being redacted, therefore analysis focussed on relative effect and data maturity. 99 NICE oncology assessments were identified, of which 63% (62) reported interim OS data with maturity <50%. Of these, 23% (14) also published an updated or final analysis of OS, including maturity level, that could be used for this analysis. 79% of the 14 submissions showed an interim maturity between 15% and 50%; their subsequent OS hazard ratio (HR) value changed within +/-20% compared to initial readout. Where interim OS was statistically significant, this was likely to remain nominally significant at final readouts. Maturity of less than 15% was associated with higher changes in relative effect by up to 80%. OS immaturity remains an area of uncertainty with payers and is managed in different ways ranging from conditional reimbursement recommendations to delaying decisions. A positive relationship between interim and updated/final OS HR was found where interim OS maturity was >= 15%, providing confidence that long term OS benefit will be demonstrated as trial data matures. In the majority of cases, delaying access due to OS data being immature or assuming there is no OS benefit, would not be justified. Conditional reimbursement or reimbursement pending additional evidence are important tools for both payers and manufacturers so that patients who can benefit from new medicines have immediate access rather than waiting for further OS readouts.

Infection with Borrelia afzelii and manipulation of the egg surface microbiota have no effect on the fitness of immature Ixodes ricinus ticks

Arthropod vectors carry vector-borne pathogens that cause infectious disease in vertebrate hosts, and arthropod-associated microbiota, which consists of non-pathogenic microorganisms. Vector-borne pathogens and the microbiota can both influence the fitness of their arthropod vectors, and hence the epidemiology of vector-borne diseases. The bacterium Borrelia afzelii, which causes Lyme borreliosis in Europe, is transmitted among vertebrate reservoir hosts by Ixodes ricinus ticks, which also harbour a diverse microbiota of non-pathogenic bacteria. The purpose of this controlled study was to test whether B. afzelii and the tick-associated microbiota influence the fitness of I. ricinus. Eggs obtained from field-collected adult female ticks were surface sterilized (with bleach and ethanol), which reduced the abundance of the bacterial microbiota in the hatched I. ricinus larvae by 28-fold compared to larvae that hatched from control eggs washed with water. The dysbiosed and control larvae were subsequently fed on B. afzelii-infected or uninfected control mice, and the engorged larvae were left to moult into nymphs under laboratory conditions. I. ricinus larvae that fed on B. afzelii-infected mice had a significantly faster larva-to-nymph moulting time compared to larvae that fed on uninfected control mice, but the effect was small (2.4% reduction) and unlikely to be biologically significant. We found no evidence that B. afzelii infection or reduction of the larval microbiota influenced the four other life history traits of the immature I. ricinus ticks, which included engorged larval weight, unfed nymphal weight, larva-to-nymph moulting success, and immature tick survival. A retrospective power analysis found that our sampling effort had sufficient power (> 80%) to detect small effects (differences of 5% to 10%) of our treatments. Under the environmental conditions of this study, we conclude that B. afzelii and the egg surface microbiota had no meaningful effects on tick fitness and hence on the R0 of Lyme borreliosis.

&lt;p&gt;&lt;strong&gt;Temperature-dependent development and reproduction of &lt;/strong&gt;&lt;strong&gt;&lt;em&gt;Oligonychus punicae&lt;/em&gt;&lt;/strong&gt;&lt;strong&gt; (Acari: Tetranychidae) on Eucalyptus&lt;/strong&gt;&lt;/p&gt;

Temperature plays an important role in the development and reproduction of mites. The present study assesses how temperature affects the biology (development and survival of immatures) and life table parameters of Oligonychus punicae. This study also determines the mite thermal requirements (thermal requirement and development base temperature). The experiments were conducted in an air-conditioned chamber under different temperatures (21, 25, 29, 33, and 37ºC). The period of each stage (egg to adult) of O. punicae at different temperatures was used to determine the thermal constant and the lower thermal limit of development. The duration of the periods of pre-oviposition, oviposition, post-oviposition, fecundity, and longevity was recorded. The life table at different temperatures was created using data from the biological cycle. There was an inverse relationship between the development time of O. punicae and temperatures. However, there was no hatching of eggs at 37ºC. All O. punicae eggs resulted in females. The survival analysis for the immature and adult (female) stages of O. punicae showed a decreased life span with increasing temperatures. For the egg-adult period, the lower thermal threshold and the thermal constant for females of O. punicae were 10.34ºC and 163.93 degree-days, respectively. Temperature affected the periods of pre-oviposition, oviposition, and fecundity of adult females of O. punicae, tending to decrease with increasing temperatures. Specific fecundity varied over the oviposition period, decreasing with increasing temperatures. The net reproduction rate decreased significantly following temperatures 21°C to 33°C. The increase in temperature results in a significantly shorter average generation time. The intrinsic rate of increase ranged from 0.15 to 0.20. The finite rates of increase were all greater than 1.00. The effects of temperature on the development of O. punicae varies according to the stage of development. The optimum temperature for O. punicae is between 25 and 29ºC.

&lt;p&gt;&lt;strong&gt;Response to thermal environment in &lt;em&gt;Tetranychus ludeni&lt;/em&gt; (Acari: Tetranychidae)&lt;/strong&gt;&lt;/p&gt;

Tetranychus ludeni Zacher is a spider mite that has invaded all continents except Antarctica and become an economically important pest around the world. Understanding the plasticity of its life history traits as a response to temperatures provides critical information for its risk analysis and management. Here we tested its response to temperatures ranging from 15 to 30ºC over two generations. We found that there was no difference in the egg hatch rate and immature survival rate across temperatures in the first generation. However, the egg hatch rate was lower and immature survival rate was higher at 30ºC in the second generation. The sex ratio (proportion of females) of resultant adults was consistent under all test temperatures in both generations except for 30ºC in the second generation which was lower. Higher temperature accelerated development in both generations but the development at the lower temperatures was faster in the second generation. Adult body size in both generations generally decreased with the increase of temperature, with females being more likely than males to adjust body size in response to temperature changes they first experienced. Temperature-dependent body size was not translated into fecundity, but larger adults lived longer. The thermal threshold was lower and degree days (DD) were greater in the second generation than in the first generation. Our findings indicate that life history traits of T. ludeni are highly flexible and adaptive to dynamic thermal environment in successive generations. Furthermore, increasing temperature elevated the intrinsic rate of increase (rm) but shortened the generation time (T) and the time to double the population size (Dt). The net population growth rate (R0) was higher at 20 and 25ºC as compared to lower and higher temperatures.

Evidence of demographic buffering in an endangered great ape: Social buffering on immature survival and the role of refined sex‐age classes on population growth rate

Theoretical and empirical research has shown that increased variability in demographic rates often results in a decline in the population growth rate. In order to reduce the adverse effects of increased variability, life-history theory predicts that demographic rates that contribute disproportionately to population growth should be buffered against environmental variation. To date, evidence of demographic buffering is still equivocal and limited to analyses on a reduced number of age classes (e.g. juveniles and adults), and on single sex models. Here we used Bayesian inference models for age-specific survival and fecundity on a long-term dataset of wild mountain gorillas. We used these estimates to parameterize two-sex, age-specific stochastic population projection models that accounted for the yearly covariation between demographic rates. We estimated the sensitivity of the long-run stochastic population growth rate to reductions in survival and fecundity on ages belonging to nine sex-age classes for survival and three age classes for female fecundity. We found a statistically significant negative linear relationship between the sensitivities and variances of demographic rates, with strong demographic buffering on young adult female survival and low buffering on older female and silverback survival and female fecundity. We found moderate buffering on all immature stages and on prime-age females. Previous research on long-lived slow species has found high buffering of prime-age female survival and low buffering on immature survival and fecundity. Our results suggest that the moderate buffering of the immature stages can be partially due to the mountain gorilla social system and the relative stability of their environment. Our results provide clear support for the demographic buffering hypothesis and its predicted effects on species at the slow end of the slow-fast life-history continuum, but with the surprising outcome of moderate social buffering on the survival of immature stages. We also demonstrate how increasing the number of sex-age classes can greatly improve the detection of demographic buffering in wild populations.

Estimating temperature effects on Drosophila suzukii life cycle parameters

Drosophila suzukii is an invasive, polyphagous pest of soft‐skinned fruits, having huge impact on fruit production in Asia, North and South America and Europe including Germany. To investigate the effect of temperature on oviposition, egg‐to‐adult development success and duration, as well as immature heat survival and adult cold survival for a German D. suzukii population several experiments were conducted under different constant temperatures in the laboratory. The resulting life cycle data were described mathematically as functions of temperature and compared with experimental results of other researchers in a summary table. Curve fittings used herein revealed that minimum, optimum and maximum temperatures are: 13.2, 26.7 and 33.6 °C for oviposition, 14.1, 22.6 and 30.0 °C for egg‐to‐adult development success, and 9.6, 27.3 and 35.7 °C for egg‐to‐adult development duration. Eggs and larvae of D. suzukii showed a reduced heat survival within the tested temperature range of 29 to 41 °C and exposure durations from 1 to 8 h. A cold survival rate of 50% was measured at e.g. −6 °C for 4 h in summer morph adults and at e.g. −6 °C for 45 h in winter morph adults confirming that the latter are more cold tolerant. Results obtained in this study for a German population of D. suzukii are similar to those obtained for populations of other origins such as Canada, Japan, Spain and USA. Thus, presumably, present data based on a German D. suzukii population can be used for a new or fine‐tune of already existing population dynamics models of D. suzukii in order to support an effective pest management strategy.

Contrasting long‐term trends in age‐specific survival of Peregrine Falcons (Falco peregrinus) in Britain using smoothed estimates of recovery probabilities

Peregrine Falcons Falco peregrinus are an iconic species of long‐standing conservation concern as a result of historical patterns of persecution and dramatic pesticide‐related population declines in many populations during the second half of the 20th century. Although the role of reduced productivity in these declines is well known, the temporal patterns in survival are much less well characterized. We estimate survival probabilities for Peregrines in Britain in the period 1975–2018 from reports of ringed birds found dead, using a non‐parametric smoothing spline to account for non‐linear temporal variation in recovery probabilities. During this time the population increased from around 350 pairs to 1628 pairs. There was little evidence of a temporal trend in the survival probabilities of adult birds since the mid‐1970s, but survival of first‐year birds appears to have decreased. Our estimates suggest that increases in the breeding population are further limited by unreported sources of mortality or by density‐dependent processes, highlighting the need for better data on immature survival and recruitment. Modelling recovery rates using a spline, rather than independent annual values, improved estimation efficiency with lower credible intervals obtained for the adult annual estimates.

Artificial rearing of the ladybird Propylea japonica on a diet containing oriental armyworm, Mythimna separata

AbstractThree artificial diets were developed and tested for their suitability for immature development and survival of the ladybird Propylea japonica (Thunberg) (Coleoptera: Coccinellidae). The artificial diet based on the oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae), resulted in 66.5% survival and was a potential food for mass rearing of P. japonica. The effect of this alternative diet was assessed independently for larval development and adult reproduction by adding various numbers of frozen aphids, and finally an artificial rearing scheme was established that could save about 80% of natural food (aphids). The results showed that the survival rate and fecundity of P. japonica reared on the best artificial diet or aphids alone were similar. A rearing scheme using mainly M. separata‐based artificial diet and a small number of frozen aphids for the mass production of P. japonica became possible.

Predation of the brown marmorated stink bug, Halyomorpha halys by the Japanese acrobat ants, Crematogaster matsumurai and Crematogaster osakensis

Halyomorpha halys (Hemiptera: Pentatomidae) is an invasive pest native to Asia that causes severe economic losses in agriculture around the world. Although chemical control is relied upon for control of this pest, better long-term solutions are needed to achieve sustainable control. Currently, information is scarce on the complex of predators regulating populations of H. halys in its native region. Through laboratory bio-assays, we investigated the predatory ability of two species of acrobat ant native to Japan, Crematogaster matsumurai and C. osakensis, and the invasive Argentine ant, Linepithema humile, presented with different immature life stages of H. halys. Results indicated that these Japanese Crematogaster ants did not prey on the H. halys eggs or affect their eclosion, but did reduce the survival of early (first, second, and third) instar nymphs. Crematogaster matsumurai limited the survival of first, second, and third instar nymphs to 0%, 40%, and 73% respectively, and C. osakensis reduced their survival to 0%, 13%, and 60%, respectively. Predation of immature H. halys by L. humile reduced the survival of all instars to zero under the laboratory conditions. These data suggest that generalist Japanese Crematogaster ants may play an important role in reducing immature survival of H. halys in their native range, but likely act additively with other natural enemies that inflict mortality on different life stages. This work demonstrates that ants deserve consideration in the development of integrated pest management strategies for H. halys.

Synthesis of Cordyceps fumosorosea-Biochar Nanoparticles and Their Effects on Growth and Survival of Bemisia tabaci (Gennadius)

Nanotechnology can offer an environmentally sustainable alternative to synthetic chemicals for pest management. Nano-formulations of different microbial pest control agents have been effective against several insect pests. Synthesis of Cordyceps fumosorosea-biochar (BC) nanoparticles and their bio-efficacy against Bemisia tabaci was observed during this study. The characterization of C. fumosorosea-BC nanoparticles through different analytical techniques showed successful synthesis of nanoparticles. UV spectroscopy showed a characteristic band of surface plasmon between 350 and 400 nm; SEM images confirmed the synthesis of spherical shaped nanoparticles; X-ray diffractogram showed strong peaks between 2θ values of 20°–25°; and atomic force microscopy (AFM) analysis revealed particle size of 49.151 nm. The bioassay studies demonstrated that different concentrations of C. fumosorosea-BC nanoparticles caused significant reduction in hatchability of B. tabaci eggs as well as survival of immatures emerging from treated eggs when compared with controls. The results also revealed that C. fumosorosea-BC nanoparticles were highly pathogenic against 2nd and 3rd instar nymphs and pupae of B. tabaci having LC50 values of 6.80, 7.45, and 8.64 ppm, respectively. The LT50 values for 20 ppm concentration of C. fumosorosea-BC nanoparticles against 2nd and 3rd instar nymphs, and pupae of B. tabaci were 3.25 ± 0.29, 3.69 ± 0.52, and 4.07 ± 0.51 days, respectively. These findings suggest that C. fumosorosea-BC nanoparticles can potentially be used in biorational B. tabaci management programs.

Physiological and reproductive fitness cost in Aedes aegypti on exposure to toxic xenobiotics in New Delhi, India

Aedes aegypti, is a well-known vector of dengue, Chikungunya and Zika at the global level. Primary use of pyrethroids as control interventions has caused the development of a considerable level of immunity in Ae. aegypti. The current study assessed the efficacy of a pyrethroid, ?-cypermethrin on the survival and various life parameters of Ae. aegypti. The larvicidal studies with ?-cypermethrin revealed the respective LC50 and LC90 values as 0.26526 mg/L and 0.60211 mg/L. The impact of LC50 level was assessed on the growth and life attributes; such as gonotrophic cycle, egg development, hatchability, development and survival of immature stages, adult longevity, reproduction rate and generation time; of fourth instar of susceptible (S) and ?-cypermethrin-exposed population (E). The exposed population showed diminished fitness as compared to the susceptible population. The individual female fecundity in susceptible population was recorded as 79.6 with 61.6% hatchability rate as compared to the 28 eggs/female and 25% hatchability in the exposed population. The mean egg hatch time in S strain increased by 2-fold in E strain. The proportion of immature survival observed in S strain was 0.88 for fourth instar to pupa (P/I), 0.94 for pupa to adult (A/P) and an overall 0.83 for fourth larva to adult (A/I), which respectively reduced to 0.32, 0.86 and 0.27 in E strain of Ae. aegypti. Likewise, the net reproductive rate, birth rate and death rate were significantly (p &lt; 0.05) higher in S than in E strain. This study demonstrates the negative impact of ?-cypermethrin on the physiological and reproductive fitness of Ae. aegypti.