High Background Risk Research Articles

Background predation risk induces anxiety-like behaviour and predator neophobia in zebrafish

Prey face a major challenge in balancing predator avoidance with other essential activities. In environments with high risk, prey may exhibit neophobia (fear of novelty) due to the increased likelihood of novel stimuli being dangerous. The zebrafish, Danio rerio, is an established model organism for many scientific studies. Although spatial and object neophobia in zebrafish have received previous attention, little is known about the role of background risk in inducing neophobia in zebrafish. Here, we present two experiments using zebrafish to explore whether background predation risk can induce anxiety-like behaviour in a novel environment and neophobic responses when exposed to a novel odour. Over five days, we repeatedly exposed zebrafish to either high background risk in the form of chemical alarm cues (i.e., injured conspecific cues that indicate a predator attack) or a low-risk water control stimulus. In Experiment 1, when tested in a novel tank, zebrafish exposed to high predation risk displayed anxiety-like responses (reduced activity and increased bottom time spent) compared to their low-risk counterparts. Moreover, high-risk individuals showed reduced intra-session habituation to the novel tank compared to low-risk individuals. In Experiment 2, high-risk individuals exhibited fear responses toward a novel odour, unlike low-risk individuals. These results reveal that short-term repeated exposures to high risk can induce anxiety-like behaviour and predator odour neophobia in zebrafish.

Use of acoustic signals in Cape fur seal mother-pup reunions: individual signature, signal propagation and pup home range.

The Cape fur seal (Arctocephalus pusillus pusillus) is one of the most colonial mammals, with colonies of up to hundreds of thousands of individuals during the breeding season. During the lactation period, mothers and pups are regularly separated as females undertake multi-day foraging trips at sea. Mothers and pups use a mutual vocal recognition system to reunite after separation. Such communication is highly constrained by both high background noise and risk of individual confusion owing to the density of seals. This study aimed to experimentally assess the acoustic features relevant for mother-pup vocal identification and the propagation properties of their calls. Playback experiments revealed that mother and pup individual vocal signatures rely on both temporal and frequency parameters: amplitude and frequency modulations, timbre and fundamental frequency (f0). This is more parameters than in any colonial species studied so far. The combinational use of acoustic features reinforces the concept that both environmental and social constraints may have acted as selective pressures on the individual vocal recognition systems. Theoretical propagation distances of mother and pup vocalisations were estimated to be below the range of distances at which mother-pup reunions can occur. This suggests that Cape fur seals may have strong abilities to extract vocal signals from the background noise, as previously demonstrated in the highly colonial king penguin. Investigating the transmission of information throughout the propagation of the signal as well as the ability of the receiving individual to decipher vocal signatures is crucial to understanding vocal recognition systems in the wild.

Effect of intrapartum epidural analgesia on rate of emergency delivery for presumed fetal compromise: nationwide registry-based cohort study.

To determine the rate of emergency delivery for presumed fetal compromise after epidural analgesia (EDA) compared with that after alternative analgesia or no analgesia, and to assess whether this rate is increased in pregnancies with reduced placental reserve. This was a nationwide registry-based cohort study of 629 951 singleton pregnancies delivered at 36 + 0 to 42 + 0 weeks of gestation that were recorded in the Dutch national birth registry between 2014 and 2018, including 120 426 cases that received EDA, 86 957 that received alternative analgesia and 422 568 that received no analgesia during labor. Pregnancies with congenital anomaly, chromosomal abnormality, fetal demise, planned Cesarean delivery, non-cephalic presentation at delivery and use of multiple forms of analgesia were excluded. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included delivery characteristics and neonatal outcome. Negative binomial regression analysis was stratified by parity and results are presented according to birth-weight centile, after adjusting for confounding. Among women who received EDA, 13.2% underwent emergency delivery for presumed fetal compromise, compared with 4.1% of women who had no analgesia (relative risk (RR), 3.23 (95% CI, 3.16-3.31)) and 7.0% of women who received alternative analgesia (RR, 1.72 (95% CI, 1.67-1.77)). Independent of birth weight, the RR of presumed fetal compromise after EDA vs no analgesia was higher in parous women (adjusted RR (aRR), 2.15 (95% CI, 2.04-2.27)) compared with nulliparous women (RR, 1.88 (95% CI, 1.84-1.94)). Stratified for parity, the effect of EDA was modified significantly by birth-weight centile (interaction P-value, < 0.001 for nulliparous and 0.004 for parous women). The emergency delivery rate following EDA was highest in those with a birth weight < 5th centile (25.2% of nulliparous and 16.6% of parous women), falling with each increasing birth-weight centile category up to the 91st -95th centile (11.8% of nulliparous and 7.2% of parous women). Intrapartum EDA is associated with a higher risk of emergency delivery for presumed fetal compromise compared with no analgesia and alternative analgesia, after adjusting for relevant confounding. The highest rate of emergency delivery for presumed fetal compromise was observed at the lowest birth-weight centiles. RRs of emergency delivery for presumed fetal compromise after EDA were modestly but consistently modified by birth-weight centile, supporting the hypothesis that the adverse effects of EDA are exacerbated by reduced placental function. While EDA provides effective pain relief during labor, alternative strategies for pain management may be preferable in pregnancies with a high background risk of fetal compromise. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The Predictive Value of Prenatal Cell-Free DNA Testing for Rare Autosomal Trisomies: A Systematic Review and Meta-analysis

ABSTRACT Noninvasive prenatal testing has been a reliable method for prenatal screening for the common autosomal trisomies for the last decade. It has been analyzed in many prospective studies for accuracy in screening for the most common trisomies—13, 18, and 21—and the technology has continued to progress. With high accuracy for common trisomies, advances are attempting to expand noninvasive prenatal testing for identifying rare autosomal trisomies, such as trisomies 7, 15, 16, and 22; sex chromosome aneuploidies; and segmental copy number variants. Although cell-free DNA (cfDNA) technology is now available to screen for these abnormalities, accuracy and detection rates have not been well studied. This systematic review analyzes and reports the diagnostic accuracy of cfDNA screening for the rare autosomal trisomies. This review included case series with 10 or more cases that reported on the accuracy of cfDNA in reporting rare autosomal trisomies that were confirmed by diagnostic results or postnatal genetic testing; the final review included 31 studies. Methodological analysis found the risk of bias to be high in most studies, with only 5 rated as high quality and low risk in all domains. All studies included in the final analyses were published between 2017 and 2022, and study populations ranged from 14 to 153,575 patients. Indications for screening and characteristics of the patients varied from study to study, with 12 studies in high-risk women, 10 studies in the general obstetric population, and 9 studies without inclusion of underlying risk factors and indications. Whole-genome sequencing was used in all studies as testing methodology. Testing timing varied and was performed anywhere from gestational week 8 to week 39. In the 3 studies that analyzed sensitivity and specificity of cfDNA testing, sensitivity ranged from 87.2% to 100%, and specificity ranged from 90.7% to 99.9%. In all 3 of these studies, there were significant limitations that led authors to acknowledge the difficulty of drawing clear conclusions about sensitivity and specificity from their data. Meta-analysis performed for positive predictive value (PPV) provided a pooled estimate of 11.46% (95% confidence interval [CI], 7.80%–15.65%). Sensitivity analysis including only studies at low risk of bias gave a PPV of 9.13% (95% CI, 2.49%–18.76%). Analysis was performed again with groups divided into high or low background risk, with a slightly higher PPV in the higher background risk group, but no significant difference between these groups (P = 0.595). Statistical heterogeneity was not explained by year of publication or baseline risk of participants but could be largely explained by rate of diagnostic follow-up. Studies with a follow-up rate of less than 50% showed a PPV of 23.69% (95% CI, 9.21%–41.94%), whereas studies with a follow-up rate greater than 50% reported a PPV of 8.80% (95% CI, 6.08%–11.90%). Based on the results of this systematic review and meta-analysis, it is likely that previously reported PPVs of cfDNA's diagnostic accuracy for detecting rare autosomal trisomies are overestimated. A reason for this could be lower follow-up rates as well as testing bias in women with high-risk cfDNA results. One reason for the low prevalence of rare autosomal trisomies is that many confirmed cases result in miscarriage before 12 weeks of gestation. Pregnancies that continue and that are not mosaic often experience major complications. The occurrence of mosaicism may impact the PPV, as mosaicism carries some risks but is sometimes not detected from cfDNA samples. This study was limited by the details included in the studies analyzed; this caused significant statistical heterogeneity, which limits the conclusions that can be drawn. In addition, detection rates may differ by type of cfDNA test, and this analysis did not stratify by type of test. The results of this analysis are consistent with previous literature on detection of rare autosomal trisomies in the general population and show that even with a high specificity and sensitivity for cfDNA testing in general, care should be taken in making clinical decisions on the part of both providers and patients in instances where a rare autosomal trisomy is suspected.

Sex and background risk influence responses to acute predation risk in Trinidadian guppies

AbstractIntraspecific sex differences in morphology, physiology, and behavior are widespread among taxa. However, despite their fundamental importance, they have been relatively understudied in the context of risk assessment. For instance, with Trinidadian guppies (Poecilia reticulata), there has been a bias toward the exclusive use of females, as males are thought to be less responsive to acute predation threats. However, there is little empirical evidence supporting this assumption. Moreover, the antipredator behavior of male guppies has been unexplored, perhaps resulting in the over-generalization of female behavior to both sexes in previous studies. Here, we conducted laboratory experiments involving wild-caught and laboratory-reared guppies. In Experiment 1, shoals of either male or female guppies from a high-predation population were tested for their response to alarm cues, novel odor, or a water control. We found that while female shoals exhibited strong antipredator responses to alarm cues and neophobic responses to novel odor, male shoals exhibited only a weak response to alarm cues and no evidence of neophobia. In Experiment 2, we exposed male and female guppies to high- or low-predation risk and then tested individuals for their responses to alarm cues, novel odor, or water control. Regardless of background risk, males did not respond to any stimulus. In contrast, low-risk females exhibited antipredator responses toward alarm cues and those from high background risk displayed neophobia. Our results suggest that females are more cautious when encountering an acute predation risk, highlighting the importance of accounting for both sexes in studies on predation.

Associations of maternal pre-pregnancy BMI and gestational weight gain with the risks of adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus

BackgroundGive the high background risk of adverse pregnancy outcomes (APOs), it is important to understand the associations of maternal pre-pregnancy body mass index (ppBMI), gestational weight gain (GWG) with APOs in women with gestational diabetes mellitus (GDM). We addressed the independent and joint associations of maternal ppBMI and GWG with APOs in Chinese women with GDM.Methods764 GDM women with singleton delivery were studied and they were stratified into three weight groups by ppBMI (underweight, normal weight and overweight/obesity) following classification standards for Chinese adults and three GWG groups (inadequate, adequate, excessive GWG) by the 2009 Institute of Medicine guidelines, respectively. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios of APOs.ResultsMaternal overweight/obesity was associated with increased odds of pregnancy-induced hypertension [PIH, adjusted odds ratio (aOR): 2.828, 95% confidence interval (CI) 1.382–5.787], cesarean delivery (CS) (aOR 2.466, 95%CI 1.694–3.590), preterm delivery (aOR 2.466, 95%CI 1.233–4.854), LGA (aOR 1.664, 95%CI 1.120–2.472), macrosomia (aOR 2.682, 95%CI 1.511–4.760) and any pregnancy complication (aOR 2.766, 95%CI 1.840–4.158) compared with healthy weight. Inadequate GWG was less likely to develop PIH (aOR 0.215, 95%CI 0.055–0.835), CS (aOR 0.612, 95%CI 0.421–0.889) and any pregnancy complication (aOR 0.628, 95%CI 0.435–0.907), but had higher risk of preterm birth (aOR 2.261, 95%CI 1.089–4.692), while excessive GWG was more vulnerable to LGA (aOR 1.929, 95%CI 1.272–2.923), macrosomia (aOR 2.753, 95%CI 1.519–4.989) and any pregnancy complication (aOR 1.548, 95%CI 1.006–2.382) as compared to adequate GWG. Furthermore, compared to normal weight mothers with adequate GWG, obese mothers with excessive GWG had the highest risk of any pregnancy complication (aOR 3.064, 95%CI 1.636–5.739).ConclusionsMaternal overweight/obesity and GWG were associated with APOs in the already high-risk settings of GDM. Obese mothers with excessive GWG may confer the greatest risk of adverse outcomes. It was very helpful to reduce the burden of APOs and benefit GDM women by promoting a healthy pre-pregnancy BMI and GWG.

Hormone replacement therapy in women with history of thrombosis or a thrombophilia.

Findings from the Women's Health Initiative (WHI) randomised placebo-controlled trial (RCT) were published at the beginning of this century. They suggested that hormone replacement therapy (HRT) use increased the risk of cardiovascular disease and venous thromboembolism including pulmonary embolism and deep vein thrombosis The findings led to a decline in HRT prescriptions and negative publicity about the use of HRT for women with significant menopausal symptoms. Subsequent studies have shown that the risk of thrombosis with HRT relates to whether estrogen is combined with a progestogen and the route of administration of estrogen. In healthy women with no background medical problems, transdermal hormone replacement is not associated with an increased risk of thrombosis. However, much less is known about the safety of various HRT preparations in women with a high background risk of thrombosis. These cases can often be challenging for clinicians with uncertainties around testing for thrombophilia, use of anticoagulation and striking a balance between the risks and benefits of prescribing HRT. This article will review the mechanism of thrombosis with differing types of HRT and present the evidence from the relevant trials. The article will also present the evidence that specifically relates to women with a personal history of thrombosis or thrombophilia (heritable and acquired) to enable clinicians to better individualise the risk assessment for each woman requesting HRT and understand the role of thrombophilia screening or concomitant anticoagulation in such situations.

Exploratory decisions of Trinidadian guppies when uncertain about predation risk.

Animals can reduce their uncertainty of predation risk by gathering new information via exploration behaviour. However, a decision to explore may also be costly due to increased predator exposure. Here, we found contextual effects of predation risk on the exploratory activity of Trinidadian guppies Poecilia reticulata in a novel environment. First, guppies were exposed to a 3-day period of either high or low background predation risk in the form of repeated exposure to either injured conspecific cues (i.e. alarm cues) or control water, respectively. A day later, guppies were moved into a testing arena with limited visual information due to structural barriers and were then presented with an acute chemical stimulus, either alarm cues (a known and reliable indicator of risk), a novel odour (an ambiguous cue), or control water. In the presence of control water, guppies from high and low background risk showed a similar willingness to explore the arena. However, high-risk individuals significantly reduced their spatial evenness, although not their movement latency, in the presence of both the alarm and novel cues. When these high-risk individuals were a member of a shoal, they became willing to explore the environment more evenly in the presence of alarm cues while remaining cautious toward the novel cue, indicating an effect of the greater uncertainty associated with the novel cue. In contrast, low-risk guppies showed a willingness to explore the arena regardless of acute threat or social context. Such contextual effects of background risk and social context highlight the complexity of exploratory decisions when uncertain.

Abstract 753: Associations of inflammatory bowel disease and subsequent cancers in the United States elderly population

Abstract Introduction: The risk for cancer may be elevated in patients with inflammatory bowel disease (IBD) due to chronic inflammation caused by IBD and/or immunosuppressive treatments. A comprehensive investigation of cancer as a complication of IBD in elderly patients is needed, as this population has a high background risk of cancer and are underrepresented in IBD studies. Methods: We performed a case-control study using Surveillance Epidemiology and End Results-Medicare linked data. Cancer cases (N=1,986,735) included all patients aged 66-99 with a first invasive neoplasm diagnosed in 1992-2015. Cancer-free controls (N=200,000) were randomly selected from Medicare and matched by sex, age, and selection year. Medicare claims containing ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes occurring at least one year prior to selection were used to identify IBD patients. We estimated odds ratios (OR) and 95% confidence intervals (CI) with logistic regression, adjusting for the matching factors, race, and the average number of physician visits per year. A Bonferroni-corrected threshold of significance was defined as p &amp;lt; 0.0003 for 156 tests. Colorectal cancer analyses were further adjusted for the average number of colorectal cancer screens per year occurring at least one year before selection. Results: IBD, CD, and UC were present in 0.80%, 0.33%, and 0.53% of cancer cases and in 0.76%, 0.30%, and 0.52% of controls, respectively. Out of 52 cancers examined, IBD was significantly associated with cancers of the small intestine (OR=2.53; 95% CI=2.14-2.99), intrahepatic (1.93; 1.48-2.52) and extrahepatic bile ducts (1.73; 1.37-2.19), rectum (1.67; 1.43-1.94), colon (1.20; 1.10-1.31), and lung (1.14; 1.07-1.23). For hematological malignancies, IBD was significantly associated with myelodysplastic syndrome (MDS) (OR=1.45; 95% CI=1.28-1.65) and diffuse large B-cell lymphoma (DLBCL) (1.28; 1.13-1.46). An inverse association was observed for IBD and cancer of the uterus (0.72; 0.62-0.83). CD was associated with cancers of the small intestine (OR= 4.21; 95% CI= 3.40-5.22), myelodysplastic syndrome (1.74; 1.44-2.11), rectum (1.60; 1.1.26-2.03), and lung (1.29; 1.16-1.43) and. UC was associated with cancers of the gastrointestinal system: intrahepatic bile ducts (1.94; 1.41-2.67), rectum (1.88; 1.57-2.25), and colon (1.38; 1.25-1.53). Conclusions: Our large population-based analysis evaluating a comprehensive range of cancers found IBD significantly associated with increased risk for cancers of the small intestine, biliary tract, colorectum, and lung. IBD was also associated with DLBCL and MDS. Positive associations with IBD and cancers of the gastrointestinal system may reflect complications of chronic inflammation, while associations with DLBCL and MDS may reflect the effect of immunosuppressive medications. Citation Format: Jeanny Wang, Monica D'Arcy, Eric Engels, Minkyo Song. Associations of inflammatory bowel disease and subsequent cancers in the United States elderly population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 753.

Exploring the threat-sensitive predator avoidance hypothesis on mate competition in two wild populations of Trinidadian guppies

The intensity of mate competition is often influenced by predation pressure. The threat-sensitive predator avoidance hypothesis predicts that prey should precisely adjust their fitness-related activities to the level of perceived acute predation risk and this effect should be stronger under high background risk. Individuals should compensate during periods of moderate risk for lost opportunities during high risk. Our study examined the interaction between acute and background predation risk on mate competition. Under laboratory conditions, we explored the effects of acute risk (low vs. high) using chemical alarm cue (AC; control (results presented in Chuard et al. (2016)) The effects of adult sex ratio on mating competition in male and female guppies (Poecilia reticulata) in two wild populations. Behav Process 129:1−10), 25 % concentration, and 100 % concentration), and population of origin (low vs. high background risk) on mate competition in guppies (Poecilia reticulata). Surprisingly, males favored courtship over forced mating under acute predation risk irrespective of background risk, potentially benefiting from a female preference for bold males. We discuss our results in the context of chemical threat-sensitivity and resource differences in defendability (e.g. mates vs. food).

Sender and receiver experience alters the response of fish to disturbance cues

Predation is a pervasive selection pressure, shaping morphological, physiological, and behavioral phenotypes of prey species. Recent studies have begun to examine how the effects of individual experience with predation risk shapes the use of publicly available risk assessment cues. Here, we investigated the effects of prior predation risk experience on disturbance cue production and use by Trinidadian guppies Poecilia reticulata under laboratory conditions. In our first experiment, we demonstrate that the response of guppies from a high predation population (Lopinot River) was dependent upon the source of disturbance cue senders (high vs. low predation populations). However, guppies collected from a low predation site (Upper Aripo River) exhibited similar responses to disturbance cues, regardless of the sender population. In our second experiment, we used laboratory strain guppies exposed to high versus low background risk conditions. Our results show an analogous response patterns as shown for our first experiment. Guppies exposed to high background risk conditions exhibited stronger responses to the disturbance cues collected from senders exposed to high (vs. low) risk conditions and guppies exposed to low risk conditions were not influenced by sender experience. Combined, our results suggest that experience with background predation risk significantly impacts both the production of and response to disturbance cues in guppies.

Combined therapy with vaginal progesterone, Arabin cervical pessary and cervical cerclage to prevent preterm delivery in high-risk women

Purpose Preterm birth is the leading cause of perinatal morbidity and mortality. Vaginal progesterone cervical cerclage and Arabin cervical pessary are considered as preventive treatments in women at risk for preterm birth. However, there is less evidence as to which of these interventions is the preferred management. The current study aims was to compare the outcome of pregnancy in women with a short cervical length managed with 4 different treatment protocols: therapy with vaginal progesterone, cervical cerclage and an Arabin cervical pessary (group A), Arabin cervical pessary and vaginal progesterone (group B), cervical cerclage and vaginal progesterone (group C), or vaginal progesterone alone (group D). Methods A retrospective cohort study of singleton pregnancies managed in three tertiary medical centers between September 2011 and December 2017. Results In the study period, 286 pregnant women underwent vaginal ultrasonography between 15 and 29 weeks gestation. They all had a short cervical length (≤25 mm). Of these, 18 (6.3%), 120 (41.9%), 38 (13.3%) and 110 (38.5%) patients received treatment classifying them into groups A, B, C, and D, respectively. A significantly higher rate of patients in group A had either a history of cervical incompetence (44.4 versus 9.2 versus 7.9 and 0.9%, respectively, p = .0001) or a cervical procedure (61.1 versus 37.5 versus 28.9 and 27.3%, respectively, p = .027) compared to patients in group B, C, and D. Despite having a shorter cervical length at recruitment in group A (median (range); 14.5 (0–25) versus 15 (0–25) versus 15.5 (0–25) and 19 (2–25) mm, respectively, p = .002) the rate of spontaneous preterm delivery <37-week gestation was similar across groups (44.4 versus 32.5 versus 36.8 versus 32.7%, respectively, p = .665). Conclusion A combined rescue therapy involving vaginal progesterone, cervical cerclage, and Arabin cervical pessary emerges as a promising management strategy in pregnant women who have a short cervical length and a high background risk for preterm delivery. This combination may prolong their pregnancy and safely bring them near term. Additional studies are needed to confirm these preliminary findings.

High background risk induces risk allocation rather than generalized neophobia in the fathead minnow

AbstractTo cope with the heterogeneous nature of predation and the trade-off between predator avoidance and foraging, prey animals have evolved several cognitive rules. One of these is the risk allocation hypothesis, which predicts that in environments with long periods of sustained high risk, individuals should decrease their antipredator effort to satisfy their metabolic requirements. The neophobia hypothesis, in turn, predicts increased avoidance of novel cues in high-risk habitats. Despite the recent interest in predator-induced neophobia across different sensory channels, tests of such generalized neophobia are restricted to a single fish taxon, the Cichlidae. Hence, we retested the generalized neophobia hypothesis in fathead minnows Pimephales promelas, a small schooling North American cyprinid fish. From hatching onward, minnows were exposed to conspecific alarm cues, which indicate predation risk, or distilled water in a split-clutch design. After 1 month, shoaling behavior was examined prior and subsequent to a mechanical predator disturbance. Fish previously exposed to elevated background risk formed compact shoals for a shorter time interval after the stimulus compared with controls. These results contrast previous studies of generalized neophobia but match the risk allocation hypothesis. Consequently, risk allocation and generalized neophobia are not ubiquitous cognitive rules but instead evolved adaptations of different taxa to their respective environments.

Who’s where? Ecological uncertainty shapes neophobic predator avoidance in Trinidadian guppies

Neophobic predator avoidance (NPA), the fear response exhibited by prey animals exposed to novel stimuli, is a plastic trait thought to be induced by exposure to elevated chronic risk of predation. Indeed, prey experiencing low levels of background risk fail to display NPA, while those experiencing high background risk do display NPA. Recent work has suggested that the trigger for inducing and maintaining NPA may not be background risk per se but rather uncertainty in the predation environment. Here, we designed two experiments on wild-caught neophobic Trinidadian guppies (Poecilia reticulata) to test the ‘uncertainty hypothesis’. In the first experiment, we tested if the diversity of novel stimuli encountered by guppies would affect the maintenance of their NPA. We found that exposure to a single novel odour once per day for 3 days was sufficient to extinguish the neophobic response to that odour (Experiment 1A) but not a new odour (Experiment 1B). However, when guppies were exposed to multiple novel odours so that each odour was encountered once a day for 3 days, they retained their NPA to both a previously encountered novel odour (Experiment 1A) and a new odour (Experiment 1B). In our second experiment, we repeatedly exposed guppies to a novel cue in a spatially predictable vs. unpredictable location and found that spatial unpredictability interfered with the reduction of NPA to that cue. Combined, our results suggest that uncertainty of risk experienced by prey in time and space shapes the retention of NPA. When prey face uncertainty, or lack of complete information, about risk in their environment, they engage in adaptive antipredator behaviours such as neophobic predator avoidance. Showing a fear response to a novel stimulus in a high-risk environment is likely adaptive if we assume that most species in that environment are threats. Here, we aim to show how uncertainty, as opposed to simply background levels of risk, may influence the maintenance of neophobic responses in prey. On the basis of two experiments, we showed that prey experiencing increased uncertainty, via increased diversity and spatial unpredictability of novel cues, maintain their neophobic responses more so than prey experiencing lower uncertainty. Understanding the effects of ecological uncertainty on prey behaviour, particularly neophobia, will shed light on how prey might respond as uncertainty increases with climate change, invasive species and anthropogenic habitat modification.

Understanding the effect of uncertainty on the development of neophobic antipredator phenotypes

Exposure of prey animals to high background risk environments generates high-risk behavioural phenotypes characterized by prey that often display transient neophobic responses to novel stimuli. To manipulate background risk, researchers have most often used chemical alarm cues from injured conspecifics because these cues provide a general indication of a high-risk environment but no information regarding the identity of the source of the threat. Here, we hypothesized that the expression of neophobia (fear of unknown stimuli) may not be the result of elevated background risk per se, but rather the result of high uncertainty associated with the predation environment. Here we showed that woodfrog, Lithobates sylvaticus, tadpoles exposed to alarm cues alone for several days subsequently displayed neophobic phenotypes. The same was true for tadpoles exposed to alarm cues paired with the odour of a new novel predator each day for several days. However, tadpoles exposed to alarm cues paired with the same predator cue everyday did not develop the neophobic phenotype. This suggests that if the predator environment is certain (i.e. the alarm cue and predator cues always coincide), then the ratio of costs to benefits of neophobia is high and limits its expression. However, if the prey's uncertainty regarding the predator environment is high (i.e. the alarm cues are often associated with new unknown predators), then the potential survival benefits of expressing neophobia likely override the costs. The prey's perception of uncertainty may be a key driver of the expression of neophobic phenotypes.

Risk of tuberculosis comparison in new users of antitumour necrosis factor-α and with existing disease-modifying antirheumatic drug therapy.

Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti-TNF) drug-associated risk of infections requires justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti-TNF-α therapy or with existing disease-modifying antirheumatic drug (DMARD) therapy. A retrospective cohort study of anti-TNF-α therapy new users (anti-TNF-α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into "mild" and "severe" disease severity as proxies for low and high background risk of infection. A total of 3640 patients were enrolled (anti-TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100000 patient-years for anti-TNF-α new users and 391.7/100000 patient-years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti-TNF-α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval [CI], 1.2-4.85), subgroup with mild disease (2.91; 1.31-6.47) and subgroup with severe disease (1.65; 0.68-4.03). Significant independent risk factors for TB were being male, age ≥60years, history of respiratory disease, glucocorticoids dose >7.5mg/d and living in a TB-prevalent region. Anti-TNF-α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders.

Trust thy neighbour in times of trouble: background risk alters how tadpoles release and respond to disturbance cues.

In aquatic environments, uninjured prey escaping a predator release chemical disturbance cues into the water. However, it is unknown whether these cues are a simple physiological by-product of increased activity or whether they represent a social signal that is under some control by the sender. Here, we exposed wood frog tadpoles (Lithobates sylvaticus) to either a high or low background risk environment and tested their responses to disturbance cues (or control cues) produced by tadpoles from high-risk or low-risk backgrounds. We found an interaction between risk levels associated with the cue donor and cue recipient. While disturbance cues from low-risk donors did not elicit an antipredator response in low-risk receivers, they did in high-risk receivers. In addition, disturbance cues from high-risk donors elicited a marked antipredator response in both low- and high-risk receivers. The response of high-risk receivers to disturbance cues from high-risk donors was commensurate with other treatments, indicating an all-or-nothing response. Our study provides evidence of differential production and perception of social cues and provides insights into their function and evolution in aquatic vertebrates. Given the widespread nature of disturbance cues in aquatic prey, there may exist a social signalling system that remains virtually unexplored by ecologists.

Background risk influences learning but not generalization of predators

The cognitive abilities of prey animals are closely linked to previous experience with predation risk. For instance, under conditions of high background risk, prey often show an enhanced ability to learn the identity of new predators. When prey learn about predators, they often use the information to make decisions about the predatory nature of unknown, but similar, species. This is referred to as generalization of predator recognition. Often, prey show the strongest response to the species they learned, and a reduced response to other species, with the phylogenetic distance between the learned predator and the other species predicting the degree of generalization. Here, we assessed whether generalization of predator recognition by woodfrog tadpoles is influenced by background level of predation risk in the environment. Given that the likelihood of making a recognition mistake (i.e. failing to respond to an unknown species that is a predator) may be greater in a high-risk environment than in a low-risk environment, we predicted that prey in high risk environments may widen their generalization window and respond with the same intensity to the learned predator and novel predators that are closely related. We found strong evidence that background risk influences the intensity of antipredator responses that prey exhibit towards learned trout predators. Moreover, tadpoles generalized their recognition to closely related trout, but the degree of generalization was independent of background risk.

Background Predation Risk and Learned Predator Recognition in Convict Cichlids: Does Risk Allocation Constrain Learning?

AbstractExposure to elevated levels of background predation risk is known to shape the behavioural response of prey organisms to known and unknown predation threats. However, less is known regarding the effects of background predation risk on predator recognition learning. Here, we test the potential effects of elevated background predation risk on the strength and retention of learned predator recognition in juvenile convict cichlids (Amatitlania nigrofasciata). In a series of laboratory trials, we exposed shoals of juvenile cichlids to conditions of elevated (vs. low) levels of background risk and then conditioned them to recognize a novel predator odour (rainbow trout, Oncorhynchus mykiss). The results of our first experiment demonstrate that despite showing reduced response intensities during initial conditioning (due to risk allocation), conditioned cichlids from high vs. low background risk show similar intensities of learned recognition when tested 24 h post‐conditioning. Moreover, elevated levels of background risk induced a predator avoidance response among unconditioned cichlids (due to induced neophobia). Our second experiment demonstrates that while we find no difference in the strength of learning when tested 24 h post‐conditioning, retention of acquired recognition is enhanced among cichlids from the high background predation risk treatment. Together, our results highlight the complex interacting effects past experience plays in shaping the response to acute predation threats.

Living on the edge: how does environmental risk affect the behavioural and cognitive ecology of prey?

Prey show remarkable plasticity across a range of traits that allow them to adapt to changes in predation risk in their local environment. While we know much about behavioural, morphological, physiological and life-history responses, we know less about how background risk alters cognitive functioning related to risk assessment. Here, we exposed wood frog tadpoles, Lithobates sylvaticus, to high- or low-risk environments for 7 days. Following this, we exposed tadpoles to one of four treatments that either continued risk, ended risk, taught tadpoles to recognize a predator or provided a false predator learning control. Tadpoles were tested for responses to predator odour, alarm cues or water either 1 day or 11 days after conditioning ended. Comparisons between conditioning treatments and test odours allowed us to assess how background risk alters a range of cognitive functions relating to risk assessment. Tadpoles that experienced high background risk responded to alarm cues with a weaker response than low-risk tadpoles, as predicted by the risk allocation hypothesis. High-risk tadpoles also developed neophobic responses to novel odours, unlike low-risk tadpoles, but displayed similar responses to a learned predator as tadpoles from low risk. When tested again 11 days later, high- and low-risk tadpoles responded equally across all treatments with the exception of learned predator responses, where high-risk tadpoles still responded strongly to the predator odour, while low-risk tadpoles did not. Our results demonstrate that recent experience with risk induces short-term cognitive plasticity in a number of functions related to risk assessment.