Extinction in multiple contexts reduces the return of extinguished responses: A multilevel meta-analysis.

Extinguished responses have been shown to reappear under several circumstances, and this reappearance is considered to model behaviors such as relapse after exposure therapy. Conducting extinction in multiple contexts has been explored as a technique to decrease the recovery of extinguished responses. The present meta-analysis aimed to examine whether extinction in multiple contexts can consistently reduce the recovery of extinguished responses. After searching in several databases, experiments were included in the analysis if they presented extinction in multiple contexts, an experimental design, and an adequate statistical report. Cohen's d was obtained for each critical comparison and weighted to obtain the sample's average weighted effect size. Analyses were then performed using a multilevel meta-analytic approach. Twenty-five studies were included, with a total sample of 37 experiments or critical comparisons. The analyses showed a large effect size for the sample, moderated by the length of conditioned stimulus exposure, type of experimental subject, and type of recovery. The robust effect of extinction in multiple contexts on relapse should encourage clinicians to consider extinction in multiple contexts as a useful technique in therapy and research.

Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA), heterogeneous biliary tumours with dismal prognosis, lacks accurate early diagnostic methods especially important for individuals at high-risk (i.e. those with primary sclerosing cholangitis [PSC]). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). METHODS: EVs from patients with isolated PSC (n = 45), concomitant PSC-CCA (n = 44), PSC who developed CCA during follow-up (PSC to CCA; n = 25), CCAs from non-PSC aetiology (n = 56), and hepatocellular carcinoma (n = 34) and healthy individuals (n = 56) were characterised by mass spectrometry. Diagnostic biomarkers for PSC-CCA, non-PSC CCA, or CCAs regardless of aetiology (Pan-CCAs) were defined and validated by ELISA. Their expression was evaluated in CCA tumours at a single-cell level. Prognostic EV biomarkers for CCA were investigated. RESULTS: High-throughput proteomics of EVs identified diagnostic biomarkers for PSC-CCA, non-PSC CCA, or Pan-CCA, and for the differential diagnosis of intrahepatic CCA and hepatocellular carcinoma, which were cross-validated by ELISA using total serum. Machine learning-based algorithms disclosed CRP/FIBRINOGEN/FRIL for the diagnosis of PSC-CCA (local disease [LD]) vs. isolated PSC (AUC = 0.947; odds ratio [OR] =36.9) and, combined with carbohydrate antigen 19-9, overpowers carbohydrate antigen 19-9 alone. CRP/PIGR/VWF allowed the diagnosis of LD non-PSC CCAs vs. healthy individuals (AUC = 0.992; OR = 387.5). It is noteworthy that CRP/FRIL accurately diagnosed LD Pan-CCA (AUC = 0.941; OR = 89.4). Levels of CRP/FIBRINOGEN/FRIL/PIGR showed predictive capacity for CCA development in PSC before clinical evidence of malignancy. Multi-organ transcriptomic analysis revealed that serum EV biomarkers were mostly expressed in hepatobiliary tissues, and single-cell RNA sequencing and immunofluorescence analysis of CCA tumours showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EV prognostic biomarkers, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively and positively with patients' survival, respectively. CONCLUSIONS: Serum EVs contain protein biomarkers for the prediction, early diagnosis, and prognostication of CCA that are detectable using total serum, representing a tumour cell-derived liquid biopsy tool for personalised medicine. IMPACT AND IMPLICATIONS: The accuracy of current imaging tests and circulating tumour biomarkers for cholangiocarcinoma (CCA) diagnosis is far from satisfactory. Most CCAs are considered sporadic, although up to 20% of patients with primary sclerosing cholangitis (PSC) develop CCA during their lifetime, constituting a major cause of PSC-related death. This international study has proposed protein-based and aetiology-related logistic models with predictive, diagnostic, or prognostic capacities by combining two to four circulating protein biomarkers, moving a step forward into personalised medicine. These novel liquid biopsy tools may allow the (i) easy and non-invasive diagnosis of sporadic CCAs, (ii) identification of patients with PSC with higher risk for CCA development, (iii) establishment of cost-effective surveillance programmes for the early detection of CCA in high-risk populations (e.g. PSC), and (iv) prognostic stratification of patients with CCA, which, altogether, may increase the number of cases eligible for potentially curative options or to receive more successful treatments, decreasing CCA-related mortality.

Evaluation and Management of Liver Transplant Candidates With Prior Nonhepatic Cancer: Guidelines From the ILTS/SETH Consensus Conference.

Liver transplant in patients with prior nonhepatic cancer is a matter of concern, needing further research, development, and consensus guidelines. This International Liver Transplantation Society/Sociedad Española De Trasplante Hepático consensus conference document focuses on the role of liver transplantation in patients with a prior history of nonhepatic cancer. This document addresses (1) the evaluation of transplant candidates with prior cancers based on the assessment of prognosis, the natural history of individual cancers, and the emerging role for circulating DNA and minimal residual disease in these patients; (2) the impact of prior treatments, including immunotherapy for prior malignancies; and (3) the surveillance of posttransplant cancer recurrence. The consensus statement is based on previously published guidelines, as well as a review of the current, relevant, published literature.

Barrier crossings and winds shape daily travel schedules and speeds of a flight generalist.

External factors such as geography and weather strongly affect bird migration influencing daily travel schedules and flight speeds. For strictly thermal-soaring migrants, weather explains most seasonal and regional differences in speed. Flight generalists, which alternate between soaring and flapping flight, are expected to be less dependent on weather, and daily travel schedules are likely to be strongly influenced by geography and internal factors such as sex. We GPS-tracked the migration of 70 lesser kestrels (Falco naumanni) to estimate the relative importance of external factors (wind, geography), internal factors (sex) and season, and the extent to which they explain variation in travel speed, distance, and duration. Our results show that geography and tailwind are important factors in explaining variation in daily travel schedules and speeds. We found that wind explained most of the seasonal differences in travel speed. In both seasons, lesser kestrels sprinted across ecological barriers and frequently migrated during the day and night. Conversely, they travelled at a slower pace and mainly during the day over non-barriers. Our results highlighted that external factors far outweighed internal factors and season in explaining variation in migratory behaviour of a flight generalist, despite its ability to switch between flight modes.

Early tacrolimus exposure does not impact long-term outcomes after liver transplantation.

BACKGROUND: Tacrolimus trough levels (TTL) during the first weeks after liver transplantation (LT) have been related with long-term renal function and hepatocellular carcinoma recurrence. Nevertheless, the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate. AIM: To evaluate the effect of TTL during the first month on the long-term outcomes after LT. METHODS: One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied. Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy. Patients were classified into 2 groups according to their mean TTL within the first month after transplantation: ≤ 10 (n = 98) and > 10 ng/mL (n = 57). Multivariate analyses were performed to assess risk factors for patient mortality. RESULTS: Mean levels within the first month post-transplant were 7.4 ± 1.7 and 12.6 ± 2.2 ng/mL in the ≤ 10 and > 10 groups, respectively. Donor age was higher in the high TTL group 62.9 ± 16.8 years vs 45.7 ± 17.5 years (P = 0.002) whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7% vs 15.8% (P = 0.02). Recipient features were generally similar across groups. After a median follow-up of 52.8 mo (range 2.8-81.1), no significant differences were observed in: Mean estimated glomerular filtration rate (P = 0.69), hepatocellular carcinoma recurrence (P = 0.44), de novo tumors (P = 0.77), new-onset diabetes (P = 0.13), or biopsy-proven acute rejection rate (12.2% and 8.8%, respectively; P = 0.50). Eighteen patients died during the follow-up and were evenly distributed across groups (P = 0.83). Five-year patient survival was 90.5% and 84.9%, respectively (P = 0.44), while 5-year graft survival was 88.2% and 80.8%, respectively (P = 0.42). Early TTL was not an independent factor for patient mortality in multivariate analyses. CONCLUSION: Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.

Carryover effects of long-distance avian migration are weaker than effects of breeding environment in a partially migratory bird.

Migration may expose individuals to a wide range of increasing anthropogenic threats. In addition to direct mortality effects, this exposure may influence post-migratory reproductive fitness. Partial migration-where a population comprises migrants and residents-represents a powerful opportunity to explore carryover effects of migration. Studies of partial migration in birds typically examine short-distance systems; here we studied an unusual system where residents breed in mixed colonies alongside long-distance trans-Saharan migrants (lesser kestrels (Falco naumanni) in Spain). Combining geolocator data, stable isotope analysis and resighting data, we examined the effects of this stark difference in migratory strategy on body condition, breeding phenology and breeding success. We monitored four colonies in two regions of southern Spain for five consecutive years (2014-2018), yielding 1962 captures, determining migratory strategy for 141 adult bird-years. Despite a 3000-km difference in distance travelled, we find no effect of strategy on breeding parameters. We find weak evidence for a short-term negative carryover effect of migration on body condition, but this was only apparent in the breeding region with lower primary productivity. Our results indicate that carryover effects of even highly divergent migratory strategies may be minimal relative to effects of conditions experienced on breeding grounds.

LEPTOSPIRA SPECIES STATUS OF CAPTIVE NONHUMAN PRIMATES AND FREE-RANGING RODENTS AT THE BARRANQUILLA ZOO, COLOMBIA, 2013.

Leptospirosis is a zoonotic disease with worldwide distribution caused by pathogenic Leptospira spp. Pathogenic Leptospira spp. are shed in urine of infected hosts and transmitted via ingestion of contaminated food or water, inoculation, inhalation of aerosolized urine, and absorption through mucous membranes. Leptospirosis is of particular concern in tropical and subtropical regions such as Barranquilla, Colombia. Recent reports indicate that in Barranquilla, rodents, dogs, and humans have a high leptospiral seroprevalence; and amongst zoo mammals, nonhuman primates have a high prevalence of Leptospira spp. infection. We therefore sought to determine whether primates in captivity at the Barranquilla Zoo were exposed to Leptospira spp. and whether there was a probable causal transmission link between the primates and peridomestic rodents. Samples were collected from 29 captive nonhuman primates, 15 free-ranging rats (Rattus rattus), and 10 free-ranging squirrels (Sciurus granatensis). Serum samples from primates, rats, and squirrels were evaluated via microagglutination test (MAT) vs 24 reference Leptospira serovars. Blood and urine from the primates and kidney tissue from the rats and squirrels were cultured in Ellinghausen-McCullough-Johnson-Harris (EMJH) medium and polymerase chain reaction (PCR) of lipL32 was performed to determine whether active infection was present. Leptospiral seroprevalence was found to be 66.7% (10/15) in rats, 60% (6/10) in squirrels, and 6.9% (2/29) in neotropical primates. Ateles hybridus and Ateles fusciceps had positive titers to serogroups Cynopteri and Ictohaemorrhagiae, respectively. Of the rodents that had antibodies against Leptospira spp., 90% of the rats and 66.7% of the squirrels corresponded to the serovar australis. Interestingly, all animals were culture and PCR negative, indicating Leptospira spp. exposure in the absence of current infection. While their status as maintenance hosts needs to be investigated further, this is the first study to show leptospiral seropositivity in red-tailed squirrels (S. granatensis).

Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, AEC, SEOM, SERAM, SERVEI y SETH.

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.

A case of COVID-19 immediately after liver transplantation: Not only bad news.

COVID-19, the illness caused by the SARS-CoV-2 virus originated in December 2019 in Wuhan, China and has caused more 3,3 million cases and more than 230,000 deaths throughout the world, with 25,000 of them only in Spain, where the first case was diagnosed on January 31st, 2020. As COVID-19 is a "new" disease, we still do not have data on prognosis or treatment in transplant patients or on how to manage immunosuppression in this complex scenario. We present a case of COVID-19 diagnosed during the early postoperative period in a recipient whose liver transplantation was performed on late March during the lockdown in Spain, with donor and recipient previously negative rRT-PCR to SARS-CoV-2. In the first post-operative week the patient suffered COVID-19 pneumonia that was treated with immunosuppression minimization, oral Hydroxycloroquine and Azithromycin with favorable outcome. The patient was discharged on POD 21 without complications. To date, few early post-liver transplantation SARS-CoV-2 infected recipients have been published, but only one was an early postoperative infection. In our case the outcome was favorable, even though it was an early post -liver transplantation COVID-19 in a frail patient.

Sex Differences in Cue Competition Effects With a Conditioned Taste Aversion Preparation.

This study aimed to test whether male and female rats might show differences in cue competition effects in a conditioned taste aversion (CTA) model. Experiment 1 tested for sex differences in overshadowing. After conditioning of a flavored compound AB or only one simple flavor A (being A and B a solution of sugar 10% and salt 1%, counterbalanced), consumption of the A solution at test was larger in the former than in the latter case only in males. Thus, the usual effect of overshadowing was observed in males but not in females. Experiment 2 examined sex differences in blocking with the same stimuli used in Experiment 1. After conditioning of AB, the consumption of B was larger for the animals that previously received a single conditioning trial with A than for those that received unpaired presentations of A and the illness. As observed in Experiment 1, the typical blocking effect appeared only in males but not in females. The present findings thus support the hypothesis that sex dimorphism might be expressed in classical conditioning, or at least, in cue competition effects such as overshadowing and blocking with a taste aversion model.

Age, sex and pre-exposure effects on acquisition and generalization of conditioned taste aversion in rats.

The main aim of the present study was to assess the effect of sex and aging in two pre-exposure learning effects, latent inhibition (LI) and perceptual learning (PL), with a conditioned taste aversion paradigm. Young adult (90 days) and aged (more than 18 months) males and females received 8 pre-exposure trials either with stimulus AX (LI conditions) or BX (PL conditions). Then, all animals received a conditioning trial with AX and two test trials, one with AX and other with BX. The level of generalization between AX and BX was assessed by means of the absolute level of consumption of BX and by the difference in consumption between both stimuli. The results showed an attenuation of latent inhibition as well a stronger generalization of conditioned taste aversion in females when generalization is inferred from the BX consumption. A facilitation of conditioning for the aged animals was also found regardless of the pre-exposed stimulus. Pre-exposures to BX resulted in little generalization, but pre-exposures to AX resulted in a very similar consumption of both compounds, indicating a strong generalization between them. Overall, the study provided novel evidence about the effect of sex and aging on taste aversion, raising at the same time some relevant questions about perceptual learning and how such pre-exposure effect has been typically assessed.

Long-Term Outcomes of Liver Transplantation in Patients With Pretransplant Renal Dysfunction Treated With Induction Therapy and Delayed Reduced De Novo Once-Daily Tacrolimus.

BACKGROUND AND AIM: Renal dysfunction is related to short- and long-term survival after liver transplantation. We present herein a retrospective analysis of our experience with liver transplantation in recipients with pretransplant renal dysfunction treated with induction therapy followed by delayed/reduced de novo once-daily tacrolimus. METHODS: Liver transplantations performed between April 2008 and August 2011 were included in this study. Pretransplant renal dysfunction was defined as estimated glomerular filtration rate <60 mL/min. Interleukin-2 receptor antagonists were used for induction therapy. Initial once-daily tacrolimus dose was 0.10 mg/kg/day or 0.07 mg/kg/day if combined with mycophenolate mofetil (MMF). Tacrolimus target trough levels were 4 to 6 ng/mL during the first post-transplant year and <4 ng/mL the rest of the follow-up. RESULTS: Nineteen patients comprised the study cohort with a median follow-up of 56.4 months (range, 11-78). Median day of tacrolimus introduction was 7 (range, 3-12). Once-daily tacrolimus was withdrawn in 6 patients (31.6%) due to evolution of renal dysfunction in all cases. At 5 years, 30% of the patients were under MMF monotherapy. Mean tacrolimus trough levels were maintained under 5 ng/mL. Mean estimated glomerular filtration rate at 5 years was 55.3 ± 12.7 mL/min. No patient needed hemodialysis or renal transplantation over the follow-up. Patient survival at 5 years was 78.9%. CONCLUSIONS: Induction therapy followed by delayed/reduced de novo once-daily tacrolimus and maintenance of low tacrolimus exposition during the follow-up is effective to maintain long-term renal function and to achieve favorable patient survival in liver transplant recipients with pretransplant renal dysfunction.

Spatial congruence between multiple stressors in the Mediterranean Sea may reduce its resilience to climate impacts.

Climate impacts on marine ecosystems may be exacerbated by other, more local stressors interacting synergistically, such as pollution and overexploitation of marine resources. The reduction of these human stressors has been proposed as an achievable way of retaining ecosystems within a "safe operating space" (SOS), where they remain resilient to ongoing climate change. However, the operability of an SOS requires a thorough understanding of the spatial distribution of these climate and human impacts. Using the Mediterranean Sea as a case study, we illustrate the spatial congruence between climate and human stressors impacting this iconic "miniature ocean" synergistically. We use long-term, spatially-explicit information on the distribution of multiple stressors to identify those highly impacted marine areas where human stressors should be prioritized for management if the resilience to climate impacts is to be maintained. Based on our spatial analysis, we exemplify how the management of an essential supporting service (seafood provision) and the conservation of a highly impacted Mediterranean sub-region (the Adriatic Sea) may benefit from the SOS framework.

How will climate change affect endangered Mediterranean waterbirds?

Global warming and direct anthropogenic impacts, such as water extraction, largely affect water budgets in Mediterranean wetlands, thereby increasing wetland salinities and isolation, and decreasing water depths and hydroperiods (duration of the inundation period). These wetland features are key elements structuring waterbird communities. However, the ultimate and net consequences of these dynamic conditions on waterbird assemblages are largely unknown. We combined regular sampling of waterbird presence through one annual cycle with in-situ data on relevant environmental predictors of waterbird distribution to model habitat selection for 69 species in a typical Mediterranean wetland network in southwestern Spain. Species associations with environmental features were subsequently used to predict changes in habitat suitability for each species under three climate change scenarios (encompassing changes in environmental predictors that ranged from 10% to 50% change as predicted by regional climatic models). Waterbirds distributed themselves unevenly throughout environmental gradients and water salinity was the most important gradient structuring the distribution of the community. Environmental suitability for the guilds of diving birds and vegetation gleaners will decline in future climate scenarios, while many small wading birds will benefit from changing conditions. Resident species and those that breed in this wetland network will also be more negatively impacted than those using this area for wintering or stopover. We provide a tool that can be used in a horizon-scanning framework to identify emerging issues in waterbird conservation and to anticipate suitable management actions.

Seasonal and circadian biases in bird tracking with solar GPS-tags.

Global Positioning System (GPS) tags are nowadays widely used in wildlife tracking. This geolocation technique can suffer from fix loss biases due to poor satellite GPS geometry, that result in tracking data gaps leading to wrong research conclusions. In addition, new solar-powered GPS tags deployed on birds can suffer from a new "battery drain bias" currently ignored in movement ecology analyses. We use a GPS tracking dataset of bearded vultures (Gypaetus barbatus), tracked for several years with solar GPS tags, to evaluate the causes and triggers of fix and data retrieval loss biases. We compare two models of solar GPS tags using different data retrieval systems (Argos vs GSM-GPRS), and programmed with different duty cycles. Neither of the models was able to accomplish the duty cycle programed initially. Fix and data retrieval loss rates were always greater than expected, and showed non-random gaps in GPS locations. Number of fixes per month of tracking was a bad criterion to identify tags with smaller biases. Fix-loss rates were four times higher due to battery drain than due to poor GPS satellite geometry. Both tag models were biased due to the uneven solar energy available for the recharge of the tag throughout the annual cycle, resulting in greater fix-loss rates in winter compared to summer. In addition, we suggest that the bias found along the diurnal cycle is linked to a complex three-factor interaction of bird flight behavior, topography and fix interval. More fixes were lost when vultures were perching compared to flying, in rugged versus flat topography. But long fix-intervals caused greater loss of fixes in dynamic (flying) versus static situations (perching). To conclude, we emphasize the importance of evaluating fix-loss bias in current tracking projects, and deploying GPS tags that allow remote duty cycle updates so that the most appropriate fix and data retrieval intervals can be selected.

Combined use of tri-axial accelerometers and GPS reveals the flexible foraging strategy of a bird in relation to weather conditions.

Tri-axial accelerometry has proved to be a useful technique to study animal behavior with little direct observation, and also an effective way to measure energy expenditure, allowing a refreshing revisit to optimal foraging theory. This theory predicts that individuals should gain the most energy for the lowest cost in terms of time and energy when foraging, in order to maximize their fitness. However, during a foraging trip, central-place foragers could face different trade-offs during the commuting and searching parts of the trip, influencing behavioral decisions. Using the lesser kestrel (Falco naumanni) as an example we study the time and energy costs of different behaviors during the commuting and searching parts of a foraging trip. Lesser kestrels are small insectivorous falcons that behave as central-place foragers during the breeding season. They can commute by adopting either time-saving flapping flights or energy-saving soaring-gliding flights, and capture prey by using either time-saving active hovering flights or energy-saving perch-hunting. We tracked 6 lesser kestrels using GPS and tri-axial accelerometers during the breeding season. Our results indicate that males devoted more time and energy to flight behaviors than females in agreement with being the sex responsible for food provisioning to the nest. During the commuting flights, kestrels replaced flapping with soaring-gliding flights as solar radiation increased and thermal updrafts got stronger. In the searching part, they replaced perch-hunting with hovering as wind speed increased and they experienced a stronger lift. But also, they increased the use of hovering as air temperature increased, which has a positive influence on the activity level of the preferred prey (large grasshoppers). Kestrels maintained a constant energy expenditure per foraging trip, although flight and hunting strategies changed dramatically with weather conditions, suggesting a fixed energy budget per trip to which they adjusted their commuting and searching strategies in response to weather conditions.

A few long versus many short foraging trips: different foraging strategies of lesser kestrel sexes during breeding.

BACKGROUND: In species with biparental care both members of the breeding pair cooperate to raise the offspring either by assisting each other in every reproductive task or by specializing in different ones. The latter case is known as reproductive role specialization. Raptors are considered one of the most role-specialized groups, but little is known about parental behavior away from the nest. Until the advent of biologgers, avian role specialization was traditionally studied with direct observations at the nest because of the difficulties of following and recording the behavior of free-ranging individuals. In this paper we analyze how the role specialization of the lesser kestrel (Falco naumanni) influences foraging movement patterns throughout the breeding season. We tracked 30 lesser kestrel breeders from two breeding colonies using high-frequency GPS-dataloggers during four consecutive breeding seasons. RESULTS: We found no differences between sexes in lesser kestrel foraging movements early in the breeding season before the formation of the breeding pair. However, we observed sexually distinct foraging movement strategies later in the breeding season once breeding pairs were formed. Lesser kestrel males performed a large number of short foraging trips while females made a few long ones. This maximized the provisioning rate by males to feed their mates and offspring. Meanwhile, lesser kestrel females spent more time at the colony than males in order to defend the nest, incubate the eggs and brood the nestlings. Females also helped their mates to provision the nestling once these had grown and required more food and less protection. Furthermore, lesser kestrels showed a sexual spatial segregation in foraging areas, with males foraging closer to the colony than females. CONCLUSIONS: The lesser kestrel responds to changes in energy demand throughout the breeding season with its foraging movement strategy, but in a different way depending on parental sex. The sexual spatial segregation observed is likely to be the result of an adaptive foraging strategy based on role specialization to reduce prey depletion close to the colony and intersexual competition in order to improve breeding success.

Favorable longterm outcomes of liver transplant recipients treated de novo with once-daily tacrolimus: Results of a single-center cohort.

The once-daily prolonged-release formulation of tacrolimus has been recently related with significant graft and patient mid-term survival advantages; however, practical information on the de novo administration after liver transplantation and longterm outcomes is currently lacking. This study is a 5-year retrospective analysis of a single-center cohort of liver transplant recipients treated de novo with once-daily tacrolimus (April 2008/August 2011). The study cohort consisted of 160 patients, including 23 with pretransplant renal dysfunction, with a median follow-up of 57.6 months (interquartile range, 46.6-69.0). Tacrolimus target trough levels were 5-10 ng/mL during the first 3 months after transplant, reducing progressively to <7 ng/mL after the first posttransplant year. Once-daily tacrolimus was withdrawn in 35 (21.8%) patients during follow-up, mostly due to renal dysfunction and/or metabolic syndrome. The biopsy-proven acute rejection rate was 12.5% with no cases of steroid-resistant rejection. The cumulative incidence of de novo diabetes, hypertension, and dyslipidemia were 16.9%, 31.2%, and 6.5%, respectively. Hepatocellular carcinoma recurrence rate was 2.8%. Renal function remained stable after the sixth month after transplant with a mean estimated glomerular filtration rate of 77.7 ± 19.6 mL/minute/1.73 m(2) at 5 years. None of our patients developed chronic kidney disease stage 4 or 5. Patient survival at 1, 3, and 5 years was 96.3%, 91.9%, and 88.3%, respectively. Overall survival of patients with Model for End-Stage Liver Disease (MELD) score > 25 points was not significantly different. In conclusion, our study suggests that immunosuppression based on de novo once-daily tacrolimus is feasible in routine clinical practice, showing favorable outcomes and outstanding longterm survival even in patients with high MELD scores. Liver Transplantation 22 1391-1400 2016 AASLD.

Extinction in multiple contexts: Effects on the rate of extinction and the strength of response recovery.

In two human predictive-learning experiments, we investigated the effects of extinction in multiple contexts on the rate of extinction and the strength of response recovery. In each experiment, participants initially received acquisition training with a target cue in one context, followed by extinction either in a different context (extinction in a single context) or in three different contexts (extinction in multiple contexts). The results of both experiments showed that conducting extinction in multiple contexts led to higher levels of responding during extinction than did extinction in a single context. Additionally, Experiment 2 showed that extinction in multiple contexts prevented ABC renewal but had no detectable impact on ABA renewal. Our results are discussed within the framework of contemporary learning theories of contextual control and extinction.