Integrating behavioural thermoregulatory strategy into the animal personality framework using the common lizard, Zootoca vivipara as a model.

The study of consistent between-individual behavioural variation in single (animal personality) and across two or more behavioural traits (behavioural syndrome) is a central topic of behavioural ecology. Besides behavioural type (individual mean behaviour), behavioural predictability (environment-independent within-individual behavioural variation) is now also seen as an important component of individual behavioural strategy. Research focus is still on the 'Big Five' traits (activity, exploration, risk-taking, sociability and aggression), but another prime candidate to integrate to the personality framework is behavioural thermoregulation in small-bodied poikilotherms. Here, we found animal personality in thermoregulatory strategy (selected body temperature, voluntary thermal maximum, setpoint range) and 'classic' behavioural traits (activity, sheltering, risk-taking) in common lizards (Zootoca vivipara). Individual state did not explain the between-individual variation. There was a positive behavioural type-behavioural predictability correlation in selected body temperature. Besides an activity-risk-taking syndrome, we also found a risk-taking-selected body temperature syndrome. Our results suggest that animal personality and behavioural syndrome are present in common lizards, both including thermoregulatory and 'classic' behavioural traits, and selecting high body temperature with high predictability is part of the risk-prone behavioural strategy. We propose that thermoregulatory behaviour should be considered with equal weight to the 'classic' traits in animal personality studies of poikilotherms employing active behavioural thermoregulation.

Phylogenetic meta-analysis reveals system-specific behavioural type-behavioural predictability correlations.

The biological significance of behavioural predictability (environment-independent within-individual behavioural variation) became accepted recently as an important part of an individual's behavioural strategy besides behavioural type (individual mean behaviour). However, we do not know how behavioural type and predictability evolve. Here, we tested different evolutionary scenarios: (i) the two traits evolve independently (lack of correlations) and (ii) the two traits' evolution is constrained (abundant correlations) due to either (ii/a) proximate constraints (direction of correlations is similar) or (ii/b) local adaptations (direction of correlations is variable). We applied a set of phylogenetic meta-analyses based on 93 effect sizes across 44 vertebrate and invertebrate species, focusing on activity and risk-taking. The general correlation between behavioural type and predictability did not differ from zero. Effect sizes for correlations showed considerable heterogeneity, with both negative and positive correlations occurring. The overall absolute (unsigned) effect size was high (Zr = 0.58), and significantly exceeded the null expectation based on randomized data. Our results support the adaptive scenario: correlations between behavioural type and predictability are abundant in nature, but their direction is variable. We suggest that the evolution of these behavioural components might be constrained in a system-specific way.

Sex-dependent increase of movement activity in the freshwater isopod Asellus aquaticus following adaptation to a predator-free cave habitat.

Populations experiencing negligible predation pressure are expected to evolve higher behavioral activity. However, when sexes have different expected benefits from high activity, the adaptive shift is expected to be sex-specific. Here, we compared movement activity of one cave (lack of predation) and three adjacent surface (high and diverse predation) populations of Asellus aquaticus, a freshwater isopod known for its independent colonization of several caves across Europe. We predicted 1) higher activity in cave than in surface populations, with 2) the difference being more pronounced in males as they are known for active mate searching behavior, while females are not. Activity was assessed both in the presence and absence of light. Our results supported both predictions: movement activity was higher in the cave than in the surface populations, particularly in males. Relaxed predation pressure in the cave-adapted population is most likely the main selective factor behind increased behavioral activity, but we also showed that the extent of increase is sex-specific.

Fine-Tuning of mTORC1-ULK1-PP2A Regulatory Triangle Is Crucial for Robust Autophagic Response upon Cellular Stress.

Autophagy-dependent cellular survival is tightly regulated by both kinases and phosphatases. While mTORC1 inhibits autophagy by phosphorylating ULK1, PP2A is able to remove this phosphate group from ULK1 and promotes the key inducer of autophagosome formation. However, ULK1 inhibits mTORC1, mTORC1 is able to down-regulate PP2A. In addition, the active ULK1 promotes PP2A via phosphorylation. We claim that these double-negative (mTORC1 -| PP2A -| mTORC1, mTORC1 -| ULK1 -| mTORC1) and positive (ULK1 -> PP2A -> ULK1) feedback loops are all necessary for the robust, irreversible decision making process between the autophagy and non-autophagy states. We approach our scientific analysis from a systems biological perspective by applying both theoretical and molecular biological techniques. For molecular biological experiments, HEK293T cell line is used, meanwhile the dynamical features of the regulatory network are described by mathematical modelling. In our study, we explore the dynamical characteristic of mTORC1-ULK1-PP2A regulatory triangle in detail supposing that the positive feedback loops are essential to manage a robust cellular answer upon various cellular stress events (such as mTORC1 inhibition, starvation, PP2A inhibition or ULK1 silencing). We confirm that active ULK1 can up-regulate PP2A when mTORC1 is inactivated. By using theoretical analysis, we explain the importance of cellular PP2A level in stress response mechanism. We proved both experimentally and theoretically that PP2A down-regulation (via addition of okadaic acid) might generate a periodic repeat of autophagy induction. Understanding how the regulation of the cell survival occurs with the precise molecular balance of ULK1-mTORC1-PP2A in autophagy, is highly relevant in several cellular stress-related diseases (such as neurodegenerative diseases or diabetes) and might help to promote advanced therapies in the near future, too.

Alleviating behavioral biases at job search: Do nudges work?

We experimentally study the effectiveness of policy interventions in reducing the negative welfare effects of behavioral biases on job search. Due to quasi-hyperbolic discounting, individuals reduce their search effort and reservation wage, while the sunk-cost fallacy makes individuals decrease their reservation wage over the search spell. We compare the effects of search cost reduction and nudging. We find that search cost reduction increases the search effort and payoffs but not the reservation wage. Conversely, nudging increases the reservation wage, but not the search effort or payoffs. Both interventions reduce the impact of the sunk-cost fallacy on the reservation wage.

Microsimulation based quantitative analysis of COVID-19 management strategies.

Pandemic management requires reliable and efficient dynamical simulation to predict and control disease spreading. The COVID-19 (SARS-CoV-2) pandemic is mitigated by several non-pharmaceutical interventions, but it is hard to predict which of these are the most effective for a given population. We developed the computationally effective and scalable, agent-based microsimulation framework PanSim, allowing us to test control measures in multiple infection waves caused by the spread of a new virus variant in a city-sized societal environment using a unified framework fitted to realistic data. We show that vaccination strategies prioritising occupational risk groups minimise the number of infections but allow higher mortality while prioritising vulnerable groups minimises mortality but implies an increased infection rate. We also found that intensive vaccination along with non-pharmaceutical interventions can substantially suppress the spread of the virus, while low levels of vaccination, premature reopening may easily revert the epidemic to an uncontrolled state. Our analysis highlights that while vaccination protects the elderly from COVID-19, a large percentage of children will contract the virus, and we also show the benefits and limitations of various quarantine and testing scenarios. The uniquely detailed spatio-temporal resolution of PanSim allows the design and testing of complex, specifically targeted interventions with a large number of agents under dynamically changing conditions.

Elevated Fasting Glucose and C-Reactive Protein Levels Predict Increased All-Cause Mortality after Elective Transcatheter Aortic Valve Implantation.

Surgical aortic valve replacement in the elderly is now being supplanted by transcatheter aortic valve implantation (TAVI). Scoring systems to predict survival after catheter-based procedures are understudied. Both diabetes (DM) and underlying inflammatory conditions are common in patients undergoing TAVI, but their impact remains understudied in this patient group. We examined 560 consecutive TAVI procedures and identified eight pre-procedural factors: age, body mass index (BMI), DM, fasting blood glucose (BG), left-ventricular ejection fraction (EF), aortic valve (AV) mean gradient, C-reactive protein levels, and serum creatinine levels and studied their impact on survival. The overall mortality rate at 30 days, 1 year and 2 years were 5.2%, 16.6%, and 34.3%, respectively. All-cause mortality was higher in patients with DM (at 30 days: 8.9% vs. 3.1%, p = 0.008; at 1 year: 19.7% vs. 14.9%, p = 0.323; at 2 years: 37.9% vs. 32.2%, p = 0.304). The presence of DM was independently associated with increased 30-day mortality (hazard ratio [HR] 5.38, 95% confidence interval [CI], 1.24-23.25, p = 0.024). BG levels within 7-11, 1 mmol/L portended an increased risk for 30-day and 2-year mortality compared to normal BG (p = 0.001 and p = 0.027). For each 1 mmol/L increase in BG 30-day mortality increased (HR 1.21, 95% CI, 1.04-1.41, p = 0.015). Reduced EF and elevated CRP were each associated with increased 2-year mortality (p = 0.042 and p = 0.003). DM, elevated BG, reduced EF, and elevated baseline CRP levels each are independent predictors of short- and long-term mortality following TAVI. These easily accessible screening parameters should be integrated into risk-assessment tools for catheter-based aortic valve replacement candidates.

The state of harm reduction in prisons in 30 European countries with a focus on people who inject drugs and infectious diseases.

BACKGROUND: People who inject drugs are often imprisoned, which is associated with increased levels of health risks including overdose and infectious diseases transmission, affecting not only people in prison but also the communities to which they return. This paper aims to give an up-to-date overview on availability, coverage and policy framework of prison-based harm reduction interventions in Europe. METHODS: Available data on selected harm reduction responses in prisons were compiled from international standardised data sources and combined with a questionnaire survey among 30 National Focal Points of the European Monitoring Centre for Drugs and Drug Addiction to determine the level of availability, estimated coverage and policy framework of the interventions. RESULTS: Information about responses to health harms in prisons is limited and heterogeneous. Cross-country comparability is hampered by diverging national data collection methods. Opioid substitution treatment (OST) is available in 29 countries, but coverage remains low (below 30% of people in need) in half of the responding countries. Needle and syringe programmes, lubricant distribution, counselling on safer injecting and tattooing/piercing are scarcely available. Testing for infectious diseases is offered but mostly upon prison entry, and uptake remains low in about half of the countries. While treatment of infections is mostly available and coverage is high for human immunodeficiency virus (HIV) and tuberculosis, hepatitis B and C treatment are less often provided. Health education as well as condom distribution is usually available, but provision remains low in nearly half of the countries. Post-release linkage to addiction care as well as to treatment of infections is available in a majority of countries, but implementation is often partial. Interventions recommended to be provided upon release, such as OST initiation, take-home naloxone and testing of infections, are rarely provided. While 21 countries address harm reduction in prison in national strategic documents, upon-release interventions appear only in 12. CONCLUSIONS: Availability and coverage of harm reduction interventions in European prisons are limited, compared to the community. There is a gap between international recommendations and 'on-paper' availability of interventions and their actual implementation. Scaling up harm reduction in prison and throughcare can achieve important individual and public-health benefits.

Habitat features and colony characteristics influencing ant personality and its fitness consequences.

Several factors can influence individual and group behavioral variation that can have important fitness consequences. In this study, we tested how two habitat types (seminatural meadows and meadows invaded by Solidago plants) and factors like colony and worker size and nest density influence behavioral (activity, meanderness, exploration, aggression, and nest displacement) variation on different levels of the social organization of Myrmica rubra ants and how these might affect the colony productivity. We assumed that the factors within the two habitat types exert different selective pressures on individual and colony behavioral variation that affects colony productivity. Our results showed individual-/colony-specific expression of both mean and residual behavioral variation of the studied behavioral traits. Although habitat type did not have any direct effect, habitat-dependent factors, like colony size and nest density influenced the individual mean and residual variation of several traits. We also found personality at the individual-level and at the colony level. Exploration positively influenced the total- and worker production in both habitats. Worker aggression influenced all the productivity parameters in seminatural meadows, whereas activity had a positive effect on the worker and total production in invaded meadows. Our results suggest that habitat type, through its environmental characteristics, can affect different behavioral traits both at the individual and colony level and that those with the strongest effect on colony productivity primarily shape the personality of individuals. Our results highlight the need for complex environmental manipulations to fully understand the effects shaping behavior and reproduction in colony-living species.

Linking behavioral thermoregulation, boldness, and individual state in male Carpetan rock lizards.

Mechanisms affecting consistent interindividual behavioral variation (i.e., animal personality) are of wide scientific interest. In poikilotherms, ambient temperature is one of the most important environmental factors with a direct link to a variety of fitness-related traits. Recent empirical evidence suggests that individual differences in boldness are linked to behavioral thermoregulation strategy in heliothermic species, as individuals are regularly exposed to predators during basking. Here, we tested for links between behavioral thermoregulation strategy, boldness, and individual state in adult males of the high-mountain Carpetan rock lizard (Iberolacerta cyreni). Principal component analysis revealed the following latent links in our data: (i) a positive relationship of activity with relative limb length and color brightness (PC1, 23% variation explained), (ii) a negative relationship of thermoregulatory precision with parasite load and risk-taking (PC2, 20.98% variation explained), and (iii) a negative relationship between preferred body temperature and relative limb length (PC3, 19.23% variation explained). We conclude that differences in boldness and behavioral thermoregulatory strategy could be explained by both stable and labile state variables. The moderate link between behavioral thermoregulatory strategy and risk-taking personality in our system is plausibly the result of differences in reproductive state of individuals or variation in ecological conditions during the breeding season.

Pd-catalyzed Suzuki-Miyaura couplings and evaluation of 13α-estrone derivatives as potential anticancer agents.

13α-Estrones are of great value owing to their potent multiple bioactivity, including anticancer activity. 3-OH or 3-OBn derivatives of 2- or 4-[(subst.) phenyl]-13α-estrone as potential antiproliferative agents have been synthesized via facile, microwave-induced, Pd-catalyzed Suzuki-Miyaura coupling. 2- or 4-Halogenated 13α-estrone derivatives have been reacted with (4-subst.)phenylboronic acids using Pd(PPh3)4 as catalyst. The nature of para substituents at the introduced phenyl group did not influence the outcome of couplings. Certain newly synthesized compounds displayed substantial antiproliferative action against human adherent cancer cell lines of gynecological origin. Important structure-activity relationships were revealed, which might be helpful in the design of potent and selective anticancer derivatives based on the hormonally inactive 13α-estrane core.

Is foraging innovation lost following colonization of a less variable environment? A case study in surface- vs. cave-dwelling Asellus aquaticus.

Behavioral innovation is a key process for successful colonization of new habitat types. However, it is costly due to the necessary cognitive and neural demands and typically connected to ecological generalism. Therefore, loss of behavioral innovativeness is predicted following colonization of new, simple, and invariable environments. We tested this prediction by studying foraging innovativeness in the freshwater isopod Asellus aquaticus. We sampled its populations along the route of colonizing a thermokarstic water-filled cave (simple, stable habitat with only bacterial mats as food) from surface habitats (variable environment, wide variety of food). The studied cave population separated from the surface populations at least 60,000 years ago. Animals were tested both with familiar and novel food types (cave food: bacterial mats; surface food: decaying leaves). Irrespective of food type, cave individuals were more likely to feed than surface individuals. Further, animals from all populations fed longer on leaves than on bacteria, even though leaves were novel for the cave animals. Our results support that cave A. aquaticus did not lose the ability to use the ancestral (surface) food type after adapting to a simple, stable, and highly specialized habitat.

Neurocognitive functions in patients with hepatitis C infection.

BACKGROUND AND PURPOSE: With improving treatment options, more attention is being paid to the neurocognitive symptoms related to hepatitis C infection (HCI). While HCI-related neurocognitive impairments are frequently subclinical, they can influence patients' quality of life and fitness to work. Objective - The aim of this study was to assess HCI patients' neurocognitive functions and explore the correlations between disease variables and neurocognitive symptoms. METHODS: The study was conducted between January 1, 2013 and December 31, 2015. All patients with HCI were included in the study who were registered at the Hepatology Outpatient Clinic of Szent István and Szent László Hospitals, met inclusion criteria and volunteered to participate. Patients' sociodemographic data and medical history were recorded in a questionnaire designed for the study. The 21-item Beck Depression Inventory was used to detect depressive symptoms. Six computerized tests were used to evaluate patients' neuropsychological functions. RESULTS: Sixty patients participated in the study. In comparison with general population standards, patients demonstrated poorer performance in several neurocognitive tests. Neuropsychological performance was correlated with age, sex, length of time since HCI diagnosis, Fibroscan score and the number of previous antiviral treatments. CONCLUSION: The study's main finding is that compared to general population standards, patients with hepatitis C virus-related disease exhibit impaired neuropsychological functioning in visuomotor and visuospatial functions, working memory, executive functions, and reaction time. Executive functions and reaction time were the most sensitive indicators for the length and severity of the disease. Deterioration in these functions has a major negative effect on work performance particularly in certain occupations.

Roll with the fear: environment and state dependence of pill bug (Armadillidium vulgare) personalities.

Most studies on animal personality evaluate individual mean behaviour to describe individual behavioural strategy, while often neglecting behavioural variability on the within-individual level. However, within-individual behavioural plasticity (variation induced by environment) and within-individual residual variation (regulatory behavioural precision) are recognized as biologically valid components of individual behaviour, but the evolutionary ecology of these components is still less understood. Here, we tested whether behaviour of common pill bugs (Armadillidium vulgare) differs on the among- and within-individual level and whether it is affected by various individual specific state-related traits (sex, size and Wolbachia infection). To this aim, we assayed risk-taking in familiar vs. unfamiliar environments 30 times along 38 days and applied double modelling statistical technique to handle the complex hierarchical structure for both individual-specific trait means and variances. We found that there are significant among-individual differences not only in mean risk-taking behaviour but also in environment- and time-induced behavioural plasticity and residual variation. Wolbachia-infected individuals took less risk than healthy conspecifics; in addition, individuals became more risk-averse with time. Residual variation decreased with time, and individuals expressed higher residual variation in the unfamiliar environment. Further, sensitization was stronger in females and in larger individuals in general. Our results suggest that among-individual variation, behavioural plasticity and residual variation are all (i) biologically relevant components of an individual's behavioural strategy and (ii) responsive to changes in environment or labile state variables. We propose pill bugs as promising models for personality research due to the relative ease of getting repeated behavioural measurements.

P2X7 Receptors Drive Poly(I:C) Induced Autism-like Behavior in Mice.

Maternal immune activation (MIA) is a principal environmental risk factor contributing to autism spectrum disorder (ASD), which compromises fetal brain development at critical periods of pregnancy and might be causally linked to ASD symptoms. We report that endogenous activation of the purinergic ion channel P2X7 (P2rx7) is necessary and sufficient to transduce MIA to autistic phenotype in male offspring. MIA induced by poly(I:C) injections to P2rx7 WT mouse dams elicited an autism-like phenotype in their offspring, and these alterations were not observed in P2rx7-deficient mice, or following maternal treatment with a specific P2rx7 antagonist, JNJ47965567. Genetic deletion and pharmacological inhibition of maternal P2rx7s also counteracted the induction of IL-6 in the maternal plasma and fetal brain, and disrupted brain development, whereas postnatal P2rx7 inhibition alleviated behavioral and morphological alterations in the offspring. Administration of ATP to P2rx7 WT dams also evoked autistic phenotype, but not in KO dams, implying that P2rx7 activation by ATP is sufficient to induce autism-like features in offspring. Our results point to maternal and offspring P2rx7s as potential therapeutic targets for the early prevention and treatment of ASD.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a neurodevelopmental psychiatric disorder caused by genetic and environmental factors. Recent studies highlighted the importance of perinatal risks, in particular, maternal immune activation (MIA), showing strong association with the later emergence of ASD in the affected children. MIA could be mimicked in animal models via injection of a nonpathogenic agent poly(I:C) during pregnancy. This is the first report showing the key role of a ligand gated ion channel, the purinergic P2X7 receptor in MIA-induced autism-like behavioral and biochemical features. We show that genetic or pharmacological inhibition of both maternal and offspring P2X7 receptors could reverse the compromised brain development and autistic phenotype pointing to new possibilities for prevention and treatment of ASD.

Maternal diet affects juvenile Carpetan rock lizard performance and personality.

Differences in both stable and labile state variables are known to affect the emergence and maintenance of consistent interindividual behavioral variation (animal personality or behavioral syndrome), especially when experienced early in life. Variation in environmental conditions experienced by gestating mothers (viz. nongenetic maternal effects) is known to have significant impact on offspring condition and behavior; yet, their effect on behavioral consistency is not clear. Here, by applying an orthogonal experimental design, we aimed to study whether increased vitamin D3 content in maternal diet during gestation (vitamin-supplemented vs. vitamin control treatments) combined with corticosterone treatment (corticosterone-treated vs. corticosterone control treatments) applied on freshly hatched juveniles had an effect on individual state and behavioral consistency of juvenile Carpetan rock lizards (Iberolacerta cyreni). We tested the effect of our treatments on (a) climbing speed and the following levels of behavioral variation, (b) strength of animal personality (behavioral repeatability), (c) behavioral type (individual mean behavior), and (d) behavioral predictability (within-individual behavioral variation unrelated to environmental change). We found higher locomotor performance of juveniles from the vitamin-supplemented group (42.4% increase), irrespective of corticosterone treatment. While activity personality was present in all treatments, shelter use personality was present only in the vitamin-supplemented × corticosterone-treated treatment and risk-taking personality was present in corticosterone control treatments. Contrary to our expectations, behavioral type was not affected by our treatments, indicating that individual quality can affect behavioral strategies without affecting group-level mean behavior. Behavioral predictability decreased in individuals with low climbing speed, which could be interpreted as a form of antipredator strategy. Our results clearly demonstrate that maternal diet and corticosterone treatment have the potential to induce or hamper between-individual variation in different components of boldness, often in interactions.

Effect of hepatitis C infection on the quality of life.

PURPOSE: To assess the quality of life (QoL) of patients with hepatitis C infection (HCI) and its correlations with demographic and clinical variables. DESIGN AND METHODS: QoL and depressive symptoms were evaluated with the validated rating instruments of the 36-item short form (SF-36) generic health survey and the second version of the self-rated Beck depression inventory (BDI-II) in a cross-sectional design and correlated with basic demographic and clinical variables, including the Fibroscan score, which indicates the severity of liver impairment. FINDINGS: A cohort of 60 HCI patients who participated in the study scored lower than the general population on all domains of the SF-36. In the multivariate correlation analysis, only the physical functioning domain of the SF-36 showed a significant correlation with age, gender, and BD-II and Fibroscan scores. IMPLICATIONS FOR CLINICAL PRACTICE: QoL is lower for patients who are older, female, and have depressive symptoms. Progression of hepatic cirrhosis is associated with lower QoL in the physical domain.

Environment-dependence of behavioural consistency in adult male European green lizards (Lacerta viridis).

Understanding the background mechanisms affecting the emergence and maintenance of consistent between-individual variation within population in single (animal personality) or across multiple (behavioural syndrome) behaviours has key importance. State-dependence theory suggests that behaviour is 'anchored' to individual state (e.g. body condition, gender, age) and behavioural consistency emerges through behavioural-state feedbacks. A number of relevant state variables are labile (e.g. body condition, physiological performance) and expected to be affected by short-term environmental change. Yet, whether short-term environmental shifts affect behavioural consistency during adulthood remains questionable. Here, by employing a full-factorial laboratory experiment, we explored if quantity of food (low vs. high) and time available for thermoregulation (3h vs. 10h per day) had an effect on activity and risk-taking of reproductive adult male European green lizards (Lacerta viridis). We focussed on different components of behavioural variation: (i) strength of behavioural consistency (repeatability for animal personality; between-individual correlation for behavioural syndrome), (ii) behavioural type (individual mean behaviour) and (iii) behavioural predictability (within-individual behavioural variation). Activity was repeatable in all treatments. Risk-taking was repeatable only in the low basking treatments. We found significant between-individual correlation only in the low food × long basking time group. The treatments did not affect behavioural type, but affected behavioural predictability. Activity predictability was higher in the short basking treatment, where it also decreased with size (≈ age). Risk-taking predictability in the short basking treatment increased with size under food limitation, but decreased when food supply was high. We conclude that short-term environmental change can alter various components of behavioural consistency. The effect could be detected in the presence/absence patterns of animal personality and behavioural syndrome and the level of individual behavioural predictability, but not in behavioural type.

HCV prevalence and risk behaviours among injectors of new psychoactive substances in a risk environment in Hungary-An expanding public health burden.

BACKGROUND: In Hungary a large increase in injecting new psychoactive substances (NPS) coincided with decreasing harm reduction efforts and rising HCV infection. We describe these, and assess changes in HCV prevalence and risk behaviours, 2011-2014, among NPS injectors, using 2011-2015 syringe exchange programme (SEP) data as a key contextual ('risk environment') variable. METHODS: We conducted repeated national sero-behavioural surveys in people who inject drugs (PWID) injecting in the last month and attending SEPs or drug treatment centres (n=399, 2011; 384, 2014), using face-to-face interviews and dried blood-spot samples. Prevalence of injected drugs and SEP coverage (2011-2015) were assessed through our national SEP monitoring system and using population size estimates. RESULTS: NPS injecting tripled among PWID attending SEPs in Hungary (2011: 26%; 2015: 80%). Among NPS injectors, HCV prevalence, sharing syringes and sharing any injecting equipment (last month), doubled (2011-2014: 37%-74%, 20%-48%, 42%-71%, respectively), significantly exceeding prevalence in other PWID groups. Among young NPS injectors (aged<25), HCV prevalence increased 7-fold (12%-76%), among new injectors (injecting<2years) 4-fold (13%-42%), coupled with high levels of equipment sharing (79% and 72% respectively). Not using a condom at last intercourse (79%), ever-imprisonment (65%) and last-year homelessness (57%) were highly prevalent among NPS injectors (2014). The number of syringes distributed per estimated PWID nationally fell from 114 to 81 (2011-2014) and dropped to 28 in 2015. CONCLUSION: NPS injectors in Hungary are at severe risk of blood-borne infections due to high levels of injecting and sexual risk behaviours within a high-risk environment, including continuously low SEP provision, imprisonment and homelessness. An HIV outbreak cannot be excluded. Stronger investment in evidence-based prevention measures, with special focus on young and new injectors, and expansion of hepatitis C treatment are urgently needed.

Correlated Observations, the Law of Small Numbers and Bank Runs.

Empirical descriptions and studies suggest that generally depositors observe a sample of previous decisions before deciding if to keep their funds deposited or to withdraw them. These observed decisions may exhibit different degrees of correlation across depositors. In our model depositors decide sequentially and are assumed to follow the law of small numbers in the sense that they believe that a bank run is underway if the number of observed withdrawals in their sample is large. Theoretically, with highly correlated samples and infinite depositors runs occur with certainty, while with random samples it needs not be the case, as for many parameter settings the likelihood of bank runs is zero. We investigate the intermediate cases and find that i) decreasing the correlation and ii) increasing the sample size reduces the likelihood of bank runs, ceteris paribus. Interestingly, the multiplicity of equilibria, a feature of the canonical Diamond-Dybvig model that we use also, disappears almost completely in our setup. Our results have relevant policy implications.