Medication use during pregnancy and the risk of gastroschisis: a systematic review and meta-analysis of observational studies.

OBJECTIVES: The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring. METHODS: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I2 statistic for heterogeneity and publication bias was calculated. RESULTS: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%). CONCLUSIONS: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.

Profile of Drug Utilization in Patients with Rare Diseases in Tuscany, Italy: A Population-Based Study.

Patients with rare diseases (RDs) generally have delayed diagnosis and misdiagnosis, which lead to inappropriate care or the need to modify treatment during the course of the disease. The medical care of RD patients can be further complicated by the presence of comorbidities. In this population-based study, we evaluated the prevalence, intensity of use, and consumption of drugs prescribed to RD patients residing in Tuscany (Italy) in the years 2008-2018. Data from the Registry of Rare Diseases of Tuscany were integrated with information retrieved from regional pharmaceutical prescription databases. The overall prevalence of drug use in the RD patients was 85.4%. Drugs for the alimentary tract and metabolism and antiinfectives for systemic use showed the highest prevalence of use, while drugs for the nervous system had the highest intensity of use only in the pediatric patients. The adults exhibited a female preponderance in terms of the prevalence of use and drug consumption in almost all the age groups and therapeutic categories. Conversely, a higher prevalence of use was observed in the male children. These results provide relevant insights into drug profiles in RD patients, representing a first step for future analyses to monitor changes in drug utilization in patients with RDs over time.

Epidemiology of aplasia cutis congenita: A population-based study in Europe.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. OBJECTIVES: This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). METHODS: Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. RESULTS: Five hundred cases were identified in the period 1998-2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams-Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. CONCLUSION: To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.

Healthcare Burden of Rare Diseases: A Population-Based Study in Tuscany (Italy).

Patients with rare diseases (RDs) need tailored, continuous, and multidisciplinary hospital care. This retrospective cohort study aimed to analyse the healthcare burden of RD patients using a multi-database approach, by linking the data of the Rare Diseases Registry of Tuscany with the regional hospital discharge database. The study population included 21,354 patients diagnosed with a RD between 1 January 2000 and 31 December 2017. The healthcare burden was evaluated for all the RDs during 2009-2018 period. The hospitalisation rate (per 1000) decreased over the years, ranging from 606.9 in 2009 (95% CI: 589.2-625.0) to 443.0 in 2018 (95% CI: 433.2-453.0). A decrease in the average length of stay (LOS) was observed in the earlier years, followed by an increase up to a steady trend (8.3 days in 2018). The patients with RDs of metabolism and the genitourinary system showed the highest hospitalisation rate (903.3 and 644.0 per 1000, respectively). The patients with rare immune system disorders and diseases of the skin and subcutaneous tissue showed the highest LOS (9.7 and 9.5 days, respectively). The methodological approach presented in this population-based study makes it possible to estimate the healthcare burden of RDs, which is crucial in the decision-making and planning aimed at improving patient care.

Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study.

Background: Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data. Methods: A total of 21 orphan drugs used in outpatient settings, approved in the European Union before or during the 2008-2018 period and involving 15 rare diseases, were included in the study. The monitored population included patients with one of the conditions surveilled by the population-based Tuscany Registry of Rare Diseases and diagnosed between 2000-2018. A multi-database approach was applied, by linking data from the registry with information collected in drug prescriptions databases. The prevalence and intensity of use were estimated for the selected orphan drugs and other non-orphan medications, used to treat the same rare disease and for which a change in the prevalence of use was hypothesized after authorization of the orphan drug. Results: For some diseases (acquired aplastic anemia, tuberous sclerosis complex, most metabolic diseases) a low prevalence of orphan drugs use was observed (range between 1.1-12.5%). Conversely, orphan drugs were frequently used in hemophilia B, Wilson disease and idiopathic pulmonary fibrosis (maximum of 78.3, 47.6 and 41.8%, respectively). For hemophilia B and Leber's hereditary optic neuropathy, there are currently no other medications used in clinical practice in addition to orphan drugs. Six orphan drugs were used for the treatment of pulmonary arterial hypertension, appearing the elective therapy for this disease, albeit with different utilization profiles (range of prevalence 1.7-55.6%). Conclusion: To the best of our knowledge, this is the first study investigating the utilization profile of orphan drugs prescribed in a defined geographical area, and providing relevant information to monitor over time potential changes in the prevalence of these medications as well as in the health care decision making.

Association between maternal body mass index and congenital anomalies: A case-control study in Tuscany (Italy).

OBJECTIVE: To investigate the relationship between prepregnancy maternal body mass index (BMI) and congenital anomalies (CAs). DESIGN: Case-control study on data collected by the registry of CAs of Tuscany (Italy) and birth certificates from 2005 to 2017. MAIN EXPOSURE: Maternal prepregnancy BMI. MAIN OUTCOME MEASURES: Any major CAs and groups of organ-specific anomalies. Odds ratios (ORs) were estimated using logistic regression models adjusted for maternal factors. RESULTS: Maternal BMI ≥25 was significantly associated with all nervous system anomalies (OR = 1.61, 95% confidence interval [95% CI] 1.13-2.29) and with neural tube defects (OR = 2.03, 95% CI 1.00-4.12); maternal underweight was significantly associated with orofacial clefts (OR = 1.67, 95% CI 1.12-2.48). After stratification by education, in the low education group, mothers with BMI ≥25 had an increased risk of nervous system anomalies (OR = 2.19, 95% CI 1.01-4.76), whereas underweight mothers had an increased risk of nervous system anomalies (OR = 3.89, 95% CI 1.44-10.53), orofacial clefts (OR = 2.59, 95% CI 1.24-5.42), and urinary anomalies (OR = 1.74, 95% CI 1.07-2.82). In the medium/high education group, the only significantly increased risk was found in mothers with BMI ≥25 for nervous system anomalies (OR = 1.50, 95% CI 1.00-2.25). CONCLUSION: Main results have shown a positive association of maternal BMI ≥25 with nervous system anomalies and maternal underweight with orofacial clefts. The study has also evidenced the impact of social status and provided clues to the role of maternal ethnic background.

Survival of patients with rare diseases: a population-based study in Tuscany (Italy).

BACKGROUND: Rare diseases (RDs) encompass a heterogeneous group of life-threatening or chronically debilitating conditions that individually affect a small number of subjects but overall represent a major public health issue globally. There are still limited data on RD burden due to the paucity of large population-based epidemiological studies. The aim of this research was to provide survival estimates of patients with a RD residing in Tuscany, Italy. METHODS: Cases collected in the Rare Diseases Registry of Tuscany with diagnosis between 1st January 2000 and 31th December 2018 were linked to the regional health databases in order to retrieve information on mortality of all subjects. Survival at 1, 5 and 10 years from diagnosis with 95% confidence intervals (CI) was estimated by sex, age class, nosological group and subgroup using the Kaplan-Meier method. The effect of sex, age and period of diagnosis (years 2000-2009 or 2010-2018) on survival was estimated using Cox proportional hazards regression. RESULTS: Survival at 1, 5 and 10 years from diagnosis was 97.3%, 88.8% and 80.8%, respectively. Respiratory diseases and peripheral and central nervous system disorders were characterized by the lowest survival at 5 and 10 years. Despite a modest higher prevalence of RDs among females (54.0% of the total), male cases had a significant increased risk of death (hazard ratio, HR 1.48, 95% CI 1.38-1.58). Cases diagnosed during 2010-2018 period had a risk of death significantly lower than those diagnosed during 2000-2009 (HR 0.81, 95% CI 0.82-0.96), especially for immune system disorders (HR 0.48, 95% CI 0.26-0.87), circulatory system diseases (HR 0.61, 95% CI 0.45-0.84) and diseases of the musculoskeletal system and connective tissue (HR 0.64, 95% CI 0.49-0.84). CONCLUSIONS: An earlier diagnosis as well as the improvement in the efficacy of treatment resulted in a decreased risk of death over the years for specific RDs. The linkage between a population-based registry and other regional databases exploited in this study provides a large and accurate mass of data capable of estimating patients' life-expectancy and increasing knowledge on the collective burden of RDs.

Sociodemographic Differences in Prenatal Diagnosis of Chromosomal Anomalies: A Population-Based Study.

Background: In Europe, about 76% of cases of chromosomal anomalies are prenatally diagnosed. Prenatal diagnosis allows more efficient planning of postnatal treatment and helps parents for an informed decision about the continuation of pregnancy. The main aim of this study was to evaluate whether the sociodemographic maternal characteristics affect the probability of prenatal diagnosis of chromosomal anomalies. Methods: Cases of chromosomal anomalies in the period 2005-2017 came from the population-based registry of congenital anomalies of Tuscany (Italy). Differences in the proportion of cases prenatally diagnosed were investigated through the following maternal characteristics: education, geographic origin and occupation. The association between cases of termination of pregnancy after prenatal diagnosis and maternal characteristics was also analysed. Odds Ratios (OR) adjusted by maternal age were calculated using logistic regression models. Results were provided for all cases of chromosomal anomalies and for Down syndrome cases. Results: A total of 1,419 cases were included in the study. Cases prenatally diagnosed were 1,186 (83.6%). We observed a higher proportion of cases not prenatally diagnosed among cases with low maternal education compared to those with high maternal education (OR = 2.16, p < 0.001) and in women from high migratory outflow countries, compared to the Italian ones (OR = 2.85, p < 0.001). For prenatally diagnosed Down syndrome cases, we observed a higher proportion of termination of pregnancy for women with low education level (OR = 4.36, p = 0.023). Conclusions: In our study evidence of differences in the probability of prenatal diagnosis of chromosomal anomalies associated with maternal education and geographic origin was found. Population-based studies investigating sociodemographic disparities can provide essential information for targeted public health programs. Further studies are recommended to monitor the impact of the increasing availability of non-invasive screening tests.

Lifestyle and sociodemographic risk factors for gastroschisis: a systematic review and meta-analysis.

BACKGROUND: Gastroschisis is strongly associated with young maternal age. This association suggests the need for further investigations on non-genetic risk factors. Identifying these risk factors is a public health priority in order to develop prevention strategies aimed at reducing the prevalence and health consequences in offspring. OBJECTIVE: To systematically assess and quantitatively synthesise the available epidemiological studies to evaluate the association between non-genetic risk factors and gastroschisis. METHODS: Literature from PubMed, EMBASE and Scopus was searched for the period 1990-2018. Epidemiological studies reporting risk estimates between lifestyle and sociodemographic risk factors and gastroschisis were included. Two pairs of reviewers independently extracted information on study characteristics following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and MOOSE (Meta-analysis Of Oservational Studies in Epidemiology) guidelines. Relative risk (RR) estimates were calculated across the studies and meta-analysis was performed using random-effects model. RESULTS: We identified 58 studies. Meta-analyses were conducted on 29 studies. Maternal smoking (RR 1.56, 95% CI 1.40 to 1.74), illicit drug use (RR 2.14, 95% CI 1.48 to 3.07) and alcohol consumption (RR 1.40, 95% CI 1.13 to 1.70) were associated with an increased risk of gastroschisis. A decreased risk among black mothers compared with non-Hispanic white mothers (RR 0.49, 95% CI 0.38 to 0.63) was found. For Hispanic mothers no association was observed. CONCLUSIONS: Exposure to smoking, illicit drugs and alcohol during pregnancy is associated with an increased risk of gastroschisis. A significantly decreased risk for black mothers was observed. Further epidemiological studies to assess the potential role of other environmental factors are strongly recommended. PROSPERO REGISTRATION NUMBER: CRD42018104284.

Annoyance Judgment and Measurements of Environmental Noise: A Focus on Italian Secondary Schools.

The effects of noise on students' health, well-being, and learning are of growing concern among both the general public and policy-makers in Europe. Several studies have highlighted the consequences of noise on children's learning and performance at school. This study investigates the relationship between noise judgment in school goers aged 11-18 and noise measurements aimed at evaluating their exposure at school. For this purpose, a questionnaire was administered to 521 individuals in 28 classrooms in eight schools of four cities in Italy, with different environmental characteristics. Using a Likert-type scale, a selected set of responses related to noise generated an Annoyance Index (AI) score for each student and a classroom median score (MAI). From the noise data acquired, a global noise score (GNS) was assigned to each classroom. A higher AI was found in industrialized areas and among younger students. No significant differences in noise judgment were found by gender. A significant inverse correlation was described between MAI and GNS, thus the better the acoustic quality of the classrooms, the less the perceived noise and annoyance. The results show that noise perception and consequent disturbance are highly correlated with classroom acoustics, and confirm that annoyance represents the most widespread subjective response to noise.

Drinking and driving among Italian adolescents: Trends over seven years (2007-2013).

In recent years, increasing attention has been paid to the issue of driving under the influence of alcohol (DUI), especially among young people. The aims of the present study were (1) to analyse the trends of DUI, riding with a driver under influence of alcohol (RWDUI) and alcohol-related road crashes (A-rC) in a nationally representative sample of students in the period 2007-2013, (2) to assess how different drinking patterns were associated with DUI and RWDUI, (3) to evaluate other influential factors (such as gender, older siblings' and friends' behaviour with alcohol) on DUI and RWDUI. Data were drawn from the cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) carried out annually in Italy. The sample size ranged from 25,555 to 40,390 students (15-19 years old). Results were stratified for students <18 years and ≥18 years old. Although a significant decreasing trend for alcohol consumption was observed only in the younger group, a significant decrease in DUI [APC (annual percent change) -9.7 in the younger and -6.4 in the older group] and in RWDUI (APC -6.7 in the younger and -4.8 in the older group) was detected. A significant decreasing trend of A-rC was observed only in the older group (APC -3.4). Three specific drinking patterns were identified: "Drinking to Excess" (DE), "Drinking with Intoxication" (DI) and "Drinking but Not to Excess" (DNE). In both age groups, the DE pattern significantly increased the likelihood of DUI, whereas the DI pattern was negatively associated, and the DNE pattern was not associated. Different results were found for RWDUI: the DE and DI patterns where significantly associated with RWDUI, whereas the DNE pattern was negatively associated. Overall, illegal substance use, parental monitoring, peers' and siblings' influence were associated with DUI and RWDUI. The change in behaviour towards DUI and RWDUI suggests a cumulative effectiveness of current alcohol policies, although further actions (greater attention to social context, law enforcement, and promotion of good practice) are needed to substantially reduce alcohol-related crashes.

Evaluation of drinking patterns and their impact on alcohol-related aggression: a national survey of adolescent behaviours.

BACKGROUND: Although there have been a wide range of epidemiological studies examining the impact of patterns of alcohol consumption among adolescents, there remains considerable variability in both defining these patterns and the ability to comprehensively evaluate their relationship to behavioural patterns. This study explores a new procedure for defining and evaluating drinking patterns and integrating well-established indicators. The composite measure is then used to estimate the impact of these patterns on alcohol-related aggressive behaviour among Italian adolescents. METHODS: Data were collected as part of the 2011 European School Survey Project on Alcohol and other Drugs (ESPAD). A national sample of 14,199 students aged 15-19 years was collected using an anonymous, self-administered questionnaire completed in a classroom setting. Drinking patterns were established using principal component analysis. Alcohol-related aggression was analysed as to its relationship to patterns of drinking, behaviour of friends towards alcohol use, substance use/abuse, school performance, family relationships and leisure activities. RESULTS: Several specific drinking patterns were identified: "Drinking to Excess" (DE), "Drinking with Intoxication" (DI) and "Drinking but Not to Excess" (DNE). A higher percentage of males were involved in alcohol-related aggression compared with females. In males, the DE and DI patterns significantly increased the likelihood of alcohol-related aggression, whereas the DNE pattern was negatively associated. Similar results were found in females, although the DI pattern was not significantly associated with alcohol-related aggression. Overall, cigarette smoking, illegal drug use, truancy, limited parental monitoring, frequent evenings spent outside of the home and peer influence associated strongly with alcohol-related aggression. CONCLUSIONS: Our findings suggest that drinking patterns, as uniquely monitored with an integrated metric, can: 1) explain drinking habits better than commonly used indicators of alcohol use and 2) provide a better understanding of behavioural risks such as alcohol-related aggression. Environmental background also appears to strongly associate with this type of aggressive behaviour.

Characteristics of alcoholics attending 'clubs of alcoholics in treatment' in Italy: a national survey.

AIMS: To provide an overview of alcoholics attending a socio-ecological treatment programme [Clubs of Alcoholics in Treatment (CATs)] and to identify factors associated with abstinence and self-perceived improvement in lifestyle. METHODS: A national sample of 7522 subjects (76% males and 24% females, mean age 53.2 ± 11.3 years ± SD) attending CATs was evaluated using a self-administered questionnaire completed at a weekly meeting in 2006. RESULTS: Of participants, >70% reported no alcohol use in the last year and around 90% indicated no use in the previous month, whereas 4% of them declared no alcohol use before club attendance. Abstinence and lifestyle improvement were related positively to the number of years of club attendance but negatively to the presence of other problems in addition to the alcohol-related one. Moreover, being older or female was associated with more likely achievement of abstinence as well as with the perception of a better lifestyle. Finally, attending the club with one or more family members was associated with achievement of better lifestyle. CONCLUSION: These data provide an overview of alcoholics attending the CAT programme and are a first step toward developing a surveillance system. In addition, on the basis of this preliminary picture further research (notably longitudinal studies) can be planned considering this method and its effectiveness.

Investigations of a simulated geomagnetic field experienced by the International Space Station on attentional performance.

We have previously reported that the exposure to an abnormal magnetic field simulating the one encountered by the International Space Station (ISS) orbiting around the Earth may enhance autonomic response to emotional stimuli. Here we report the results of the second part of that study which tested whether this field also affects cognitive functions. Twenty-four volunteers participated in the study, 12 exposed to the natural geomagnetic field and 12 to the magnetic field encountered by ISS. The test protocol consisted of a set of eight tests chosen from a computerized test battery for the assessment of attentional performance. The duration of exposure was 90 min. No effect of exposure to ISS magnetic field was observed on attentional performance.

Simulation of the geomagnetic field experienced by the International Space Station in its revolution around the Earth: effects on psychophysiological responses to affective picture viewing.

There is evidence suggesting that exposure to an abnormal magnetic environment may produce psychophysiological effects related to abnormalities in responses to stress. This may be of relevance for space medicine where astronauts are exposed to a magnetic field different from that exerted by the Earth. Aim of this study was to assess how the exposure of the head to a magnetic field simulating the one encountered by the International Space Station (ISS) during a single orbit (90 min) around the Earth affects the cardiovascular and psychophysiological parameters. Twenty-four human volunteers were studied double blindly in random order under sham and magnetic exposure. During exposure, the persons were shown a set of pictures of different emotional content while subjective self-rating, skin conductance (SC), blood pressure (BP), and heart rate (HR) were measured. In addition, BP, HR, and tooth pain threshold were assessed before and after exposure. While subjects were under magnetic exposure, skin conductance was strongly differentiated (F(2,36)=22.927; p=0.0001), being high during emotionally involving (positive and negative) pictures and low during neutral pictures. Conversely, when subjects were under sham exposure, no significant differences were observed. There was, however, a trend for higher heart rate during picture viewing under magnetic exposure as compared to sham exposure. No effects were found for the other variables. These results suggest that an abnormal magnetic field that simulates the one encountered by ISS orbiting around the Earth may enhance autonomic response to emotional stimuli.

Effects of 50 Hz electromagnetic fields on electroencephalographic alpha activity, dental pain threshold and cardiovascular parameters in humans.

Recent studies indicate that exposure to extremely low frequency magnetic fields (ELF MFs) influences human electroencephalographic (EEG) alpha activity and pain perception. In the present study we analyse the effect on electrical EEG activity in the alpha band (8-13 Hz) and on nociception in 40 healthy male volunteers after 90-min exposure of the head to 50 Hz ELF MFs at a flux density of 40 or 80 microT in a double-blind randomized sham-controlled study. Since cardiovascular regulation is functionally related to pain modulation, we also measured blood pressure (BP) and heart rate (HR) during treatment. Alpha activity after 80 microT magnetic treatment almost doubled compared to sham treatment. Pain threshold after 40 microT magnetic treatment was significantly lower than after sham treatment. No effects were found for BP and HR. We suggest that these results may be explained by a modulation of sensory gating processes through the opioidergic system, that in turn is influenced by magnetic exposure.

Effects of magnetic field exposure on open field behaviour and nociceptive responses in mice.

Results of previous studies have shown that nociceptive sensitivity in male C57 mice is enhanced by exposure to a regular 37 Hz or an irregularly varying (<1 Hz) electromagnetic field. In order to test whether these fields affect more generally mouse behaviour, we placed Swiss CD-1 mice in a novel environment (open field test) and exposed them for 2 h to these two different magnetic field conditions. Hence, we analysed how duration and time course of various behavioural patterns (i.e. exploration, rear, edge chew, self-groom, sit, walk and sleep) and nociceptive sensitivity had been affected by such exposure. Nociceptive sensitivity was significantly greater in magnetically treated mice than in controls. The overall time spent in exploratory activities was significantly shorter in both magnetically treated groups (< 1 Hz, 33% and 37 Hz, 29% of total time), than in controls (42%). Conversely, the time spent in sleeping was markedly longer in the treated groups (both 27% of total time) than in controls (11%). These results suggest that exposure to altered magnetic fields induce a more rapid habituation to a novel environment.