Impact of Anxiety During Hospitalization on the Clinical Outcome of Patients With Osteoporotic Thoracolumbar Vertebral Fracture.

STUDY DESIGN: Multicenter prospective cohort study. OBJECTIVES: Anxiety in combination with osteoporotic vertebral compression fractures (OVCFs) of the spine remains understudied. The purpose of this study was to analyze whether anxiety has an impact on the short-term functional outcome of patients with an OVCF. Furthermore, a direct impact of the fracture on the patient's anxiety during hospitalization should be recognized. METHODS: All inpatients with an OVCF of the thoracolumbar spine from 2017 to 2020 were included. Trauma mechanism, analgetic medication, anti-osteoporotic therapy, timed-up-and-go test (TuG), mobility, Barthel index, Oswestry-Disability Index (ODI) and EQ5D-5L were documented.For statistical analysis, the U test, chi-square independence test, Spearman correlation, General Linear Model for repeated measures, Bonferroni analysis and Wilcoxon test were used. The item anxiety/depression of the EQ5D-5L was analyzed to describe the patients' anxiousness. RESULTS: Data from 518 patients from 17 different hospitals were evaluated. Fracture severity showed a significant correlation (r = .087, P = .0496) with anxiety. During the hospital stay, pain medication (P < .001), anti-osteoporotic medication (P < .001), and initiation of surgical therapy (P < .001) were associated with less anxiety. The anxiety of a patient at discharge was negatively related to the functional outcomes at the individual follow-up: TuG (P < .001), Barthel index (P < .001), ODI (P < .001) and EQ5D-5L (P < .001). CONCLUSIONS: Higher anxiety is associated with lower functional outcome after OVCF. The item anxiety/depression of the EQ5D-5L provides an easily accessible, quick and simple tool that can be used to screen for poor outcomes and may also offer the opportunity for a specific anxiety intervention.

Performance of Field's Stain Compared with Conventional Giemsa Stain for the Rapid Detection of Blood Microfilariae in Gabon.

Filarial infections caused by Loa loa and Mansonella perstans are a considerable public health burden in rural regions of Central Africa. Rapid diagnostic tools for the detection of microfilariae in the blood are needed. Field's stain is a rapid staining technique for microscopic slides originally established for malaria diagnostics. It requires less than 1 minute of staining compared with conventional staining protocols requiring at least 15 to 20 minutes for staining and could thus significantly accelerate diagnostics for human filariasis. Here we evaluated Field's stain as a rapid staining technique in comparison to Giemsa stain for the detection of microfilariae in peripheral blood. Blood smears were collected from 175 participants residing in the region of Lambaréné and Fougamou, Gabon. Each participant's samples were stained in parallel with Field's stain and conventional Giemsa stain. Slides were then microscopically assessed and compared for qualitative and quantitative results by a blinded assessor for the two endemic filarial blood pathogens M. perstans and L. loa. Field's stain shows excellent diagnostic performance characteristics for L. loa microfilariae compared with Giemsa staining. Concordance was favorable for M. perstans although lower than for L. loa. Field's stain offers a rapid alternative to Giemsa stain for detection of L. loa microfilariae in thick blood smears. This could help accelerate diagnostics of blood filarial pathogens in mass screening programs or resource constrained health care institutions with high patient load.

Preclinical and phase I studies of KA2237, a selective and potent inhibitor of PI3K ß/δ in relapsed refractory B cell lymphoma.

PI3-kinase p110δ is mainly expressed in lymphocytes and is an attractive therapeutic target in B cell lymphomas. Targeting p110ß may further suppress tumor growth and overcome escape mechanisms. KA2237 is an oral, potent, dual p110ß/p110δ inhibitor. In preclinical studies, KA2237 inhibited p110ß- and p110δ-dependent AKT activation and suppressed proliferation of diverse hematological and epithelial tumors. Twenty-one patients received KA2237 in a first-in-human phase I study (NCT02679196; diffuse large B cell, n = 8; follicular, n = 5; mantle cell, n = 3; chronic lymphocytic leukemia/small lymphocytic lymphoma, n = 3; marginal zone, n = 1; Waldenstrom's, n = 1). Median age 69; median prior therapies 3. Eighty-six percent of patients experienced treatment-related adverse events (TRAEs). Forty-three percent of patients experienced grade ≥3 TRAEs, with rash (n = 3), pneumonia (n = 3), transaminitis (n = 2), and pneumonitis (n = 2) being most common. Thirty-three percent discontinued treatment due to adverse events. KA2237 induced objective responses in indolent and aggressive lymphoma (overall response rate 37%; complete response n = 4, partial response n = 3).

Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness.

BACKGROUND: Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. METHODS: The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. RESULTS: The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X22 = 69, P < 0.0001) and the gametocyte prevalence (LRT X22 = 54, P < 0.0001). In addition, the proportion of infectious feeds (LRT X22 = 61, P < 0.0001) and the prevalence of oocysts among exposed mosquitoes (LRT X22 = 22.8, P < 0.001) was reduced when mosquitoes were fed on blood from treated children compared to untreated controls. The addition of AZ to SPAQ was associated with an increased proportion of infectious feeds (LRT X21 = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX22 = 330, P < 0.0001). CONCLUSION: This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention.

Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors.

PURPOSE: Inhibition of histone deacetylase 6 (HDAC6) is predicted to deliver both direct antitumor activity and modulation of the antitumor immune response. This study describes the development of a novel HDAC6 inhibitor. PATIENTS AND METHODS: KA2507 was characterized in HDAC biochemical and cellular target engagement assays and in preclinical efficacy models of melanoma and colorectal cancer. In a phase I study, KA2507 was administered orally using a 3+3 dose-escalation design (NCT03008018). RESULTS: KA2507 is a potent and selective inhibitor of HDAC6 (biochemical IC50 = 2.5 nmol/L). Preclinical models demonstrated antitumor efficacy in syngeneic tumor-bearing mice, with translational studies highlighting modulation of the antitumor immune response. Twenty patients were treated in a phase I study. KA2507 was well tolerated; dose-limiting toxicity was not observed up to the maximum dose administered. Pharmacokinetic profiling supported twice-daily oral dosing. Pharmacodynamic analysis demonstrated selective HDAC6 target engagement in peripheral blood cells, free from off-target class I HDAC activity. Stable disease was the best clinical response (7 patients). Three of these patients (adenoid cystic carcinoma, n = 2; rectal adenocarcinoma, n = 1) had prolonged disease stabilization that lasted for 16.4, 12.6, and 9.0 months, respectively. CONCLUSIONS: KA2507 is a potent and selective inhibitor of HDAC6 showing antitumor efficacy and immune modulatory effects in preclinical models. In a phase I study, KA2507 showed selective target engagement, no significant toxicities, and prolonged disease stabilization in a subset of patients. Further clinical studies of KA2507 are warranted, as a single agent or, preferably, combined with other immuno-oncology drugs.

Distinct signaling routes mediate intercellular and intracellular rhizobial infection in Lotus japonicus.

Rhizobial infection of legume roots during the development of nitrogen-fixing root nodules can occur intracellularly, through plant-derived infection threads traversing cells, or intercellularly, via bacterial entry between epidermal plant cells. Although it is estimated that around 25% of all legume genera are intercellularly infected, the pathways and mechanisms supporting this process have remained virtually unexplored due to a lack of genetically amenable legumes that exhibit this form of infection. In this study, we report that the model legume Lotus japonicus is infected intercellularly by the IRBG74 strain, recently proposed to belong to the Agrobacterium clade of the Rhizobiaceae. We demonstrate that the resources available for L. japonicus enable insight into the genetic requirements and fine-tuning of the pathway governing intercellular infection in this species. Inoculation of L. japonicus mutants shows that Ethylene-responsive factor required for nodulation 1 (Ern1) and Leu-rich Repeat Receptor-Like Kinase (RinRK1) are dispensable for intercellular infection in contrast to intracellular infection. Other symbiotic genes, including nod factor receptor 5 (NFR5), symbiosis receptor-like kinase (SymRK), Ca2+/calmodulin dependent kinase (CCaMK), exopolysaccharide receptor 3 (Epr3), Cyclops, nodule inception (Nin), nodulation signaling pathway 1 (Nsp1), nodulation signaling pathway 2 (Nsp2), cystathionine-ß-synthase (Cbs), and Vapyrin are equally important for both entry modes. Comparative RNAseq analysis of roots inoculated with IRBG74 revealed a distinctive transcriptome response compared with intracellular colonization. In particular, several cytokinin-related genes were differentially regulated. Corroborating this observation, cyp735A and ipt4 cytokinin biosynthesis mutants were significantly affected in their nodulation with IRBG74, whereas lhk1 cytokinin receptor mutants formed no nodules. These results indicate a differential requirement for cytokinin signaling during intercellular rhizobial entry and highlight distinct modalities of inter- and intracellular infection mechanisms in L. japonicus.

The Impacts of Unrecognized Language and Cultural Barriers During an Educational and Training Activity.

Language and cultural barriers are associated with poor health outcomes. Communication is arguably the most important variable associated with a successful educational and training Global Health Engagement (GHE) and often unrecognized even when attempts are made to address this barrier. Madagascar's GHE activity improved after the addition of local Malagasy translation to fully translated official French instruction.

Vestibular Modulation of Long-Term Potentiation and NMDA Receptor Expression in the Hippocampus.

Loss of vestibular function is known to cause spatial memory deficits and hippocampal dysfunction, in terms of impaired place cell firing and abnormal theta rhythm. Based on these results, it has been of interest to determine whether vestibular loss also affects the development and maintenance of long-term potentiation (LTP) in the hippocampus. This article summarizes and critically reviews the studies of hippocampal LTP following a vestibular loss and its relationship to NMDA receptor expression, that have been published to date. Although the available in vitro studies indicate that unilateral vestibular loss (UVL) results in reduced hippocampal field potentials in CA1 and the dentate gyrus (DG), the in vivo studies involving bilateral vestibular loss (BVL) do not. This may be due to the differences between UVL and BVL or it could be a result of in vitro/in vivo differences. One in vitro study reported a decrease in LTP in hippocampal slices following UVL; however, the two available in vivo studies have reported different results: either no effect or an increase in EPSP/Population Spike (ES) potentiation. This discrepancy may be due to the different high-frequency stimulation (HFS) paradigms used to induce LTP. The increased ES potentiation following BVL may be related to an increase in synaptic NMDA receptors, possibly increasing the flow of vestibular input coming into CA1, with a loss of selectivity. This might cause increased excitability and synaptic noise, which might lead to a degradation of spatial learning and memory.

Dorsal, but not ventral, hippocampal inactivation alters deliberation in rats.

When facing a choice at a decision point in a maze, rats often display hesitations, pauses and reorientations. Such "vicarious trial and error" (VTE) behavior is thought to reflect decision making about which choice option is best, and thus a deliberation process. Although deliberation relies on a wide neural network, the dorsal hippocampus appears to play a prominent role through both its neural activity and its dynamic interplay with other brain areas. In contrast, the involvement of the ventral hippocampus in deliberation is unexplored. Here, we compared directly the effects of dorsal (dHPC) and ventral intermediate (vHPC) hippocampal inactivations induced by intracerebral muscimol injections on VTE behavior as a model of deliberation. To this aim, we analyzed VTE events as rats were required to switch strategy to a new unlearned reward rule. We used a protocol in which task performance in muscimol-injected animals was minimally altered so as to evidence specific effects on VTE behavior. Our results show subtle alterations in VTE behavior following dHPC, but not vHPC, inactivations, therefore suggesting a specific contribution of the dorsal hippocampus to deliberation through its role in prospective evaluation of future actions.

Retrograde Induction of phyB Orchestrates Ethylene-Auxin Hierarchy to Regulate Growth.

Exquisitely regulated plastid-to-nucleus communication by retrograde signaling pathways is essential for fine-tuning of responses to the prevailing environmental conditions. The plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) has emerged as a stress signal transduced into a diverse ensemble of response outputs. Here, we demonstrate enhanced phytochrome B protein abundance in red light-grown MEcPP-accumulating ceh1 mutant Arabidopsis (Arabidopsis thaliana) plants relative to wild-type seedlings. We further establish MEcPP-mediated coordination of phytochrome B with auxin and ethylene signaling pathways and uncover differential hypocotyl growth of red light-grown seedlings in response to these phytohormones. Genetic and pharmacological interference with ethylene and auxin pathways outlines the hierarchy of responses, placing ethylene epistatic to the auxin signaling pathway. Collectively, our findings establish a key role of a plastidial retrograde metabolite in orchestrating the transduction of a repertoire of signaling cascades. This work positions plastids at the zenith of relaying information coordinating external signals and internal regulatory circuitry to secure organismal integrity.

First molecular detection of Mycoplasma wenyonii and the ectoparasite biodiversity in dairy water buffalo and cattle in Bohol, Philippines.

Hemoplasmosis caused by Mycoplasma spp. have been associated with major economic losses in the global dairy production. Hemoplasma studies in the Philippines are limited despite its potential impact. This study mainly aimed to detect the presence of hemoplasma species in dairy water buffaloes and cattle and know their ectoparasite biodiversity in Bohol, Philippines. Detection of Mycoplasma spp. was performed using peripheral blood smear examination (PBSE) and standard PCR using whole blood samples collected from 100 dairy water buffaloes and 40 dairy cattle. Available records on the average annual, monthly and daily milk production were compared between PCR-positive and PCR-negative animals. Ectoparasites were manually collected and identified. While PBSE results were all negative, PCR testing showed that 80% (80 water buffaloes and 32 cattle) were positive for Mycoplasma spp. On the other hand, a total of 1436 ectoparasites were collected (609 Haematopinus and 827 Rhipicephalus spp.). DNA sequencing revealed that obtained sequences (193 bp) from 7 animals were 99.5 to 100% similar to registered Mycoplasma wenyonii sequences. The study reports the first molecular characterization of M. wenyonii in the Philippines and probably the first detection in dairy water buffaloes in Southeast Asia.

Using MRI to predict the fate of excitotoxic lesions in rats.

Excitotoxic lesions are frequently used to assess the role of cerebral structures in cognitive processes in rodents. However, the precise site and extent of these lesions remain unknown without histological verifications. Using a 7-Teslas MRI system and a T2-weighted turbo-RARE sequence, MR images were acquired at several time points following NMDA lesions (1h, 6h, 24h, 48h, 1 week and 2 weeks). NMDA infusions into the parenchyma induced a clear and delineable hyperintense signal from 1h up to 1-week post-surgery. Hyperintensity volumes were compared with NeuN and Cresyl violet histological quantifications of the lesion magnitude. NMDA-induced hypersignal is observed as soon as 1h post-injection and is a reliable estimate of the presence (or absence) of a lesion. Compared to NeuN, Cresyl violet staining underestimates the extent of the lesion in significant proportions. The MRI hyperintensity generated by NMDA instillation into the parenchyma can be used as a powerful tool to confirm the diffusion of the drug into the cerebral tissue, to ascertain the locus of injection and predict with a high success rate the fate of NMDA lesions as soon as 1h post-surgery. This approach could be very useful in a large variety of lesion studies in rodents.

Interplay of the two ancient metabolites auxin and MEcPP regulates adaptive growth.

The ancient morphoregulatory hormone auxin dynamically realigns dedicated cellular processes that shape plant growth under prevailing environmental conditions. However, the nature of the stress-responsive signal altering auxin homeostasis remains elusive. Here we establish that the evolutionarily conserved plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) controls adaptive growth by dual transcriptional and post-translational regulatory inputs that modulate auxin levels and distribution patterns in response to stress. We demonstrate that in vivo accumulation or exogenous application of MEcPP alters the expression of two auxin reporters, DR5:GFP and DII-VENUS, and reduces the abundance of the auxin-efflux carrier PIN-FORMED1 (PIN1) at the plasma membrane. However, pharmacological intervention with clathrin-mediated endocytosis blocks the PIN1 reduction. This study provides insight into the interplay between these two indispensable signaling metabolites by establishing the mode of MEcPP action in altering auxin homeostasis, and as such, positioning plastidial function as the primary driver of adaptive growth.

Mother-to-child HIV-transmission prevention programs in a sub-Saharan African setting: The Gabonese experience.

In many developing countries, mothers' awareness remains a challenge despite the scaling up of antenatal care and programs preventing mother-to-child (MTC) HIV transmission. The present study was done in Libreville, Gabon where all antenatal care (delivery included) is free of charge. Here we assessed the timing of antenatal antiretroviral (ARV) prophylaxis initiation, HIV-exposed infants' age at their first postnatal HIV check visit and investigated the association between mothers' awareness or knowledge on their ARV therapy and infants' HIV infection. We interviewed HIV-positive mothers on their first and subsequent laboratory visits to investigate infants' HIV status and tested infants for HIV RNA and antibody between 2012 and 2014. We established that (1) of 718 HIV-positive mothers, only 6% were fully aware and knew what ARV treatment they were on during pregnancy; (2) half of the women (54%) start their antenatal ARV prophylaxis initiation during the second trimester of pregnancy; (3) 64% of HIV-exposed infants had their first HIV infection screening between birth and three months of age; (4) the overall prevalence of HIV infection in infants born from infected mothers was 8.9%; and (5) infants born from mothers uncertain about taking prophylactic ARV therapy were 13.3 times more likely to be infected by HIV than infants born from mothers certain about taking prophylactic ARV therapy. In conclusion, the study showed that despite free antenatal care, early access and adherence to components of MTC, HIV transmission preventive care remains unsatisfactory.

Phylloporus and Phylloboletellus are no longer alone: Phylloporopsis gen. nov. (Boletaceae), a new smooth-spored lamellate genus to accommodate the American species Phylloporus boletinoides.

The monotypic genus Phylloporopsis is described as new to science based on Phylloporus boletinoides. This species occurs widely in eastern North America and Central America. It is reported for the first time from a neotropical montane pine woodland in the Dominican Republic. The confirmation of this newly recognised monophyletic genus is supported and molecularly confirmed by phylogenetic inference based on multiple loci (ITS, 28S, TEF1-α, and RPB1). A detailed morphological description of P. boletinoides from the Dominican Republic and Florida (USA) is provided along with colour images of fresh basidiomata in habitat, line drawings of the main anatomical features, transmitted light microscopic images of anatomical features and scanning electron microscope images of basidiospores. The taxonomic placement, ecological requirements and distribution patterns of P. boletinoides are reviewed and the relationships with phylogenetically related or morphologically similar lamellate and boletoid taxa such as Phylloporus, Phylloboletellus, Phyllobolites and Bothia are discussed.

Coevolving MAPK and PID phosphosites indicate an ancient environmental control of PIN auxin transporters in land plants.

Plant growth flexibly adapts to environmental conditions, implying cross-talk between environmental signalling and developmental regulation. Here, we show that the PIN auxin efflux carrier family possesses three highly conserved putative mitogen-activated protein kinase (MAPK) sites adjacent to the phosphorylation sites of the well-characterised AGC kinase PINOID, which regulates the polar localisation of PINs and directional auxin transport, thereby underpinning organ growth. The conserved sites of PIN1 are phosphorylated in vitro by two environmentally activated MAPKs, MPK4 and MPK6. In contrast to AGC kinases, MAPK-mediated phosphorylation of PIN1 at adjacent sites leads to a partial loss of the plasma membrane localisation of PIN1. MAPK-mediated modulation of PIN trafficking may participate in environmental adjustment of plant growth.

Ventral Midline Thalamus Is Necessary for Hippocampal Place Field Stability and Cell Firing Modulation.

The reuniens (Re) and rhomboid (Rh) nuclei of the ventral midline thalamus are reciprocally connected with the hippocampus (Hip) and the medial prefrontal cortex (mPFC). Growing evidence suggests that these nuclei might play a crucial role in cognitive processes requiring Hip-mPFC interactions, including spatial navigation. Here, we tested the effect of ReRh lesions on the firing properties and spatial activity of dorsal hippocampal CA1 place cells as male rats explored a familiar or a novel environment. We found no change in the spatial characteristics of CA1 place cells in the familiar environment following ReRh lesions. Contrariwise, spatial coherence was decreased during the first session in a novel environment. We then investigated field stability of place cells recorded across 5 d both in the familiar and in a novel environment presented in a predefined sequence. While the remapping capacity of the place cells was not affected by the lesion, our results clearly demonstrated a disruption of the CA1 cellular representation of both environments in ReRh rats. More specifically, we found ReRh lesions to produce (1) a pronounced and long-lasting decrease of place field stability and (2) a strong alteration of overdispersion (i.e., firing variability). Thus, in ReRh rats, exploration of a novel environment appears to interfere with the representation of the familiar one, leading to decreased field stability in both environments. The present study shows the involvement of ReRh nuclei in the long-term spatial stability of CA1 place fields.SIGNIFICANCE STATEMENT Growing evidence suggest that the ventral midline thalamic nuclei (reuniens and rhomboid) might play a substantial role in various cognitive tasks including spatial memory. In the present article, we show that the lesions of these nuclei impair the spatial representations encoded by CA1 place cells of both familiar and novel environments. First, reduced variability of place cell firing appears to indicate an impairment of attentional processes. Second, impaired stability of place cell representations could explain the long-term memory deficits observed in previous behavioral studies.

Timing of Breeding in an Ecologically Trapped Bird.

In human-modified environments, organisms may prefer to use habitats where their reproductive performance is lower compared to alternative options. Many such ecological traps occur in seasonally changing environments. Although the timing of breeding has been shown to impact reproductive performance in a variety of organisms, it has never been considered as a potential mechanism underlying ecological traps. We address this issue with a migratory bird, the red-backed shrike, breeding in a human-modified, farmland-forest landscape. Shrikes prefer breeding in forest clear-cuts where their reproductive performance is lower than in less attractive farmland. We compared brood size and quality of early (first broods) and delayed breeders (replacement broods) between the two habitats. We found a stronger seasonal decrease in reproductive performance in preferred forest clear-cuts than in farmland. Food resources were slightly more abundant in forest than in farmland at the beginning of the season but depleted more steeply in forest by the end of the breeding season. By contrast, the phenotypic quality of breeders did not decline over the course of the season in either habitat. This is the first report that the timing of breeding relative to the seasonal change in key resources may play a significant role in explaining low reproductive performance in ecological traps.

Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans.

Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions. Well-defined clinical diagnostic criteria and risk factors are also missing. This paper summarizes key data interpretation challenges, practical considerations, model limitations, and the need for an integrated risk assessment. As demonstrated through selected initiatives to address other types of toxicities, opportunities exist however for improvement, especially through better concerted efforts at harmonization of current, emerging and novel in vitro systems or through the establishment of strategies for implementation of preclinical DILI models across the pharmaceutical industry. Perspectives on the incorporation of newer technologies and the value of precompetitive consortia to identify useful practices are also discussed.

Nest Predation Deviates from Nest Predator Abundance in an Ecologically Trapped Bird.

In human-modified environments, ecological traps may result from a preference for low-quality habitat where survival or reproductive success is lower than in high-quality habitat. It has often been shown that low reproductive success for birds in preferred habitat types was due to higher nest predator abundance. However, between-habitat differences in nest predation may only weakly correlate with differences in nest predator abundance. An ecological trap is at work in a farmland bird (Lanius collurio) that recently expanded its breeding habitat into open areas in plantation forests. This passerine bird shows a strong preference for forest habitat, but it has a higher nest success in farmland. We tested whether higher abundance of nest predators in the preferred habitat or, alternatively, a decoupling of nest predator abundance and nest predation explained this observed pattern of maladaptive habitat selection. More than 90% of brood failures were attributed to nest predation. Nest predator abundance was more than 50% higher in farmland, but nest predation was 17% higher in forest. Differences between nest predation on actual shrike nests and on artificial nests suggested that parent shrikes may facilitate nest disclosure for predators in forest more than they do in farmland. The level of caution by parent shrikes when visiting their nest during a simulated nest predator intrusion was the same in the two habitats, but nest concealment was considerably lower in forest, which contributes to explaining the higher nest predation in this habitat. We conclude that a decoupling of nest predator abundance and nest predation may create ecological traps in human-modified environments.