Maniola jurtina) comparing nectar use, interactions and flights in the refuge zone before and after mowing. Densities of grassland butterflies in this zone doubled on average after mowing. The density of females of M. jurtina increased on average fourfold, while males showed a more modest increase. In line with the idea of increased scramble competition in the refuge zone after mowing, M. jurtina increased the time spent on nectar feeding, the preferred nectar source was visited more frequently, and females made more use of non-preferred nectar sources. Maniola jurtina did not interact more with conspecifics after mowing, but interactions lasted longer. Flight tracks did not change in linearity, but were faster and shorter after mowing. After mowing, only a part of the local grassland butterflies moved to the uncut refuge zone. The resulting concentration effect alters the time allocated to different activities, nectar use and movements. These aspects have been largely ignored for agri-environmental schemes and grassland management in nature reserves and raise questions about optimal quantities and quality of uncut refuge sites for efficient conservation of grassland arthropods in agricultural landscapes.Sparing zones from mowing has been proposed, and applied, to improve local conditions for survival and reproduction of insects in hay meadows. However, little is known about the efficiency of refuge zones and the consequences for local populations. We studied population densities of butterflies before and after mowing in the refuge zone of 15 meadows in 2009 and 2011. We also studied the behaviour of the meadow brown ( Agriculture has strongly intensified since the 1950s with well-documented negative impacts on biodiversity . Semi-naExtensive grassland management has become a conservation practice in protected areas to control ecological succession of open habitats. Although disturbance, like mowing, is essential to keep semi-natural grasslands from successional development towards shrubland, mowing regimes may also result in increased direct and indirect mortality of grassland fauna, especially invertebrates ,9. DirecMowing regimes that leave particular zones uncut have been recommended ,12,14. THere we address the practice of leaving refuge strips unmown in hay meadows under agri-environmental schemes focusing on butterflies. We tested the hypothesis of increased use of the uncut refuge zones after mowing. This is often assumed, but rarely tested. After mowing, the majority of the surface of a meadow is cleared from floral nectar resources. This may induce dispersal away from the meadow, but also a concentration effect in the refuge zone. The latter case may in turn alter the living conditions for butterflies (and other insects) in the refuge. Depending on the surface of the refuge and its resources relative to the consumer populations, this may provide scope for further indirect, (sub)lethal effects of mowing regimes. Potential mechanisms include increased competition for nectar , increasManiola jurtina L. Second, we tested to what extent butterfly life changed in refuge zones by comparing behaviour and resource use  before and after mowing in M. jurtina. Assuming increased scramble competition, we predicted that M. jurtina butterflies spended more time feeding after mowing. Rewards per flower visit were likely to be smaller, among-butterfly interactions more frequent and flower visits shorter on average. Under this scenario of increased scramble competition for the preferred nectar, M. jurtina was predicted to use less-preferred nectar plants more frequently in the refuge after mowing. Finally, we tested the prediction of altered flight pathways with shorter flight bouts in the refuge after mowing.Butterflies are popular study species in the context of agri-environmental schemes (AES), but most studies on these schemes focus on agricultural fields rather than on grasslands –26. AES-Study sites were located in a 10 x 10 km area in Belgium . The landscape mainly consists of forest and grassland, both pastures and hay meadows. We collected data in 15 different hay meadows of various size (range: 0.7–15 ha). All sites were under agri-environmental scheme agreement, which means that meadows cannot be mown before June 15. The sites were located on private lands, and owners gave permission to conduct the study on their lands. The agreement includes limited or no use of manure and bans the use of pesticides. Hay must be removed after mowing and at least 5–10% of the meadow should be left uncut. The location of the unmown refuge zone is allowed to vary between years. Generally, the unmown zone is located on the edge of the meadow and is long and narrow . During our study, all sites were mown, but not grazed.Maniola jurtina. This satyrine is a widespread grassland species, but recent data in the framework of the European grassland butterfly index suggest a decline at the European scale [Poaceae; adults visit several flower species [M. jurtina is not territorial, i.e. males do not defend a specific perching spot as in Pararge aegeria for instance [We recorded several species of specialist grassland butterflies and generalist butterflies, which may be found in meadows but are not confined to this habitat (as defined in ). The foan scale . It is san scale . In Belgan scale . Caterpi species ,30. Male species . Males pinstance . Femalesinstance  and moreinstance ,35. Our Butterfly numbers were counted in ten sites in 2009 (June 18–August 4) and in seven in 2011 (June 9–August 2), two of which were also studied in 2009, between 10.00 h and 17.00 h on sunny days  on 5 m x 20 m transects . Each site was visited three times before and three times after mowing. The mean number of days (± SE) between the date of the transect count of the three visits and the date of mowing was 7.6 ± 0.6 days before mowing and 4.7 ± 0.7 days after.M. jurtina. In 2011, meteorological conditions forced farmers to mow at the beginning of July, one month after the beginning of the flight period. Hence, the combined data set provides a reasonable level of overlap between mowing dates and the butterfly flight season without any particular phenological bias. Additionally, we performed independent transect counts throughout the study period in 2011 in one site that was never mown, to provide reference phenology curves without mowing. This reference site, located within the study area, was visited on 7 days and three transects were done at each date. Butterflies were recorded in the same categories  as for mown sites [Sites were chosen to reflect variation in mowing date relative to butterfly phenology. In 2009, the studied meadows were mown 2 weeks (end of June), 4 weeks (mid July) and 6 weeks (end of July) after emergence of wn sites .Coenonympha pamphilus, Maniola jurtina, Aphantopus hyperantus, Melanargia galathea, Pyronia tithonus, Papilio machaon, Thymelicus lineola, T. sylvestris, Thecla betulae, Heodes tityrus, Polyommatus icarus and Lycaena phlaeas) and habitat generalist species  [M. jurtina we also recorded sex and activity .Future refuge zones were delineated before the flight period and we did one transect count per visit per site in this zone before and after mowing. The abundance of all butterfly species was recorded and we distinguished between grassland (e.g. erflies) . For M. 2 plots. One inflorescence or one solitary flower equalled one flower unit. The sum of all flower units in all plots of each transect was used as an estimate of the total nectar supply. We also calculated the ratio of the abundance of Centaurea jacea L. relative to the abundance of other flower species. In our sites, C. jacea is the preferred nectar source of M. jurtina and of several other butterflies.Floral nectar supply was quantified in each meadow every 10 days. Along each transect, all flower units were counted by plant species in ten randomly placed 1-mM. jurtina. We used two nectar plant species: the preferred C. jacea and Trifolium pratense L. The latter is typically used in the absence of C. jacea. The individuals of both nectar species were grown in pots under outdoor conditions. Plants that were introduced in the field were clipped back to a single inflorescence, protected by an exclosure bag to avoid insect visits prior to the experiment. We placed one flowering plant of each species next to each other in the refuge zone. The exclosure bags were removed and flower visits were recorded during 1 h by video camera (JVC Everio). As we could not distinguish between males and females in every sequence, we used total visit rate by M. jurtina. We repeated the experiment on 5 days before mowing (between June 25 and July 16) and on 4 days after mowing (between August 1 and August 12).In 2009, we introduced a number of potted nectar plants to one of our sites  on sunny days between 10.00 h and 17.00 h and recorded flower head visits by In the same year and site, we tracked the behaviour of 41 males (28 before and 13 after mowing) and 68 females (39 before and 29 after mowing) on sunny days between 10.00 h and 17.00 h. Butterflies were caught with a hand net and individually marked on the ventral hind wing. After marking, the butterfly was returned to the net and was released after a 1-min recovery period. Next, the butterfly was tracked for 10 min from a distance of 1 m. The trajectory was recorded by a handheld GPS . The following behavioural categories were recorded using a digital voice recorder (Olympus VN-5500PC): flying, feeding, basking, resting, mating, egg laying  and intraspecific interactions , which were used as a measure of the intensity of scramble competition. For flower visits, the nectar plant species was also recorded. Before mowing, tracking was performed in the whole site, since no butterfly stayed within the future refuge zones, which did not differ from the rest of the meadow at that time and were smaller than an individual butterfly’s home range. After mowing, tracking was always performed in the unmown refuge zones, since butterflies stayed in these zones. If a tracked individual left the uncut zone, we continued to follow it up to 10 min.M. jurtina males and females.To describe the relative butterfly abundance in the unmown site, we fitted second-order polynomials to the densities observed in the transects at the different dates by least square differences for grassland butterflies, habitat generalist species and for M. jurtina) and date2 were used as continuous, fixed factors. Butterfly group , mowing stage (before or after mowing) and the interaction term were used as fixed factors. Site, year and the site x mowing interaction were introduced as random factors. For the analysis of M. jurtina densities, we applied the same model, with sex as a factor instead of butterfly group.Butterfly densities in the refuge zone before and after mowing were analysed by mixed models on ln . Date  . CovariaA mixed binomial logistic model with a logit link (SAS glimmix procedure) was used to analyse the frequency of individuals observed feeding. Covariance parameters were estimated by RSPL . DenomiC. jacea or T. pratense) and the interaction term as fixed factors, in R 2.15.1 [For the analysis of visitation rates on introduced flower heads, we performed a zero-inflated Poisson regression with mowing treatment, nectar plant species . We included only those flights that fulfilled at least one of three criteria: i) the flight lasted longer than 3 s; ii) it covered more than 30 cm; or iii) the activity before the flight differed from the activity after the flight. After mowing, we selected only the flight bouts that remained within the unmown zone; the mown meadow is a very different environment from the refuge and alters flight paths from typical foraging to straight dispersal flight . For fliM. jurtina reached their peak abundance in 2011 at the end of June and decreased in abundance afterwards, while males were observed at lower densities throughout the observation period . The effect of mowing had a sex-specific effect, explaining the highly significant interaction effect . Before C. jacea , but absent for T. pratense .Camera observations on potted nectar plants in the field before and after mowing also showed an increase in feeding rate in the uncut strips after mowing . InteresM. jurtina, 68 females and 41 males, together they performed 400 nectaring visits: 162 (90 before mowing and 72 after) for females and 238 (118 before and 120 after mowing) for males, respectively. Behavioural data indicated that after mowing a larger part of their time was spent feeding ; females spent 24.3% of their time to nectaring before mowing and 36.8% after, while males allocated respectively 23.3% and 44.8% of their time . The ratio between the abundance of C. jacea and other flower species did not change between the two periods (22.6% before mowing and 23.5% after).After mowing, females visited other species than the preferred Before mowing, ovipositing females flew down into the grass to reach ground level, laid a single egg before flying away and repeating the sequence. Five females out of the 39 that were tracked were observed ovipositing and they laid a total of 16 eggs. After mowing, females almost always left the refuge zone and flew over variable distances in the mown zone before landing and ovipositing on a support or on bare ground in the mown zone. Then they flew further away to repeat the sequence before ultimately flying back to the refuge zone. Egg laying was the only activity observed in the mown zone after mowing. A total of 25 ovipositions performed by eight females  were observed, 21 of which were outside of the refuge zone.M. jurtina males and other butterflies (148 before and 87 after mowing). Males did not interact more frequently with other butterflies after mowing (mean number of interactions during an observation session ± SE: 2.23 ± 0.42) than before (1.89 ± 0.31) . However, intraspecific interactions lasted on average longer after mowing .We observed 235 interactions between Both sexes tended to switch between activities more frequently after mowing  .After mowing, single flight bouts of both males and females were significantly shorter; this was true for both total and net displacement. Flight bouts were also faster, but did not differ in linearity , Fig 4. M. jurtina), several of our results from behavioural observations point at higher levels of competition for resources in the refuge zone after mowing. These aspects have not been fully appreciated by conservation biologists and practitioners so far.The basic challenge of mowing management from an animal conservation viewpoint is dealing with the compromise between short-term negative effects and long-term beneficial effects of keeping the vegetation in favorable condition, although other organisms may benefit from later successional stages of the vegetation . The issThe density of grassland butterflies in the refuge zone was almost doubled after mowing, whereas the density of habitat generalist butterflies remained stable. In 2011, mowing occurred after the butterfly abundance peak, hence the increased density in the refuge zone cannot be attributed to phenology. An increase in density in the refuge zone after mowing has recently been shown for grass-feeding insects  and theM. jurtina, higher densities after mowing are in line with the predicted concentration effect in the uncut refuge zone. At least in 2011, since peak abundance had already been reached before mowing, seasonal effects could be excluded as a cause for this increase. Some of the individuals could be immigrants from nearby meadows, but such an effect is likely to be more important if several meadows are mown simultaneously in a resource-poor landscape. However, Dover et al. [For grassland butterflies like r et al.  did not M. jurtina females we observed on average a fourfold increase. The discrepancy between the predicted and observed densities suggests significant losses for local populations, although with the current data we cannot discriminate between mortality and emigration. Direct killing due to hay cutting has been shown for several organisms [If we assume i) homogeneous habitat quality and butterfly abundance within a meadow and ii) that all grassland butterflies of a particular meadow would move to the uncut zone after mowing, then the increase in density should be inversely proportional to the part of the meadow left uncut. In our study, on average 10% of the meadows was left uncut, which would lead to the prediction of a tenfold increase in grassland butterfly density for the refuge zone. However, we observed on average only a doubling of the densities; for rganisms , but rarrganisms ,51.As our results suggest, unmown refuge zones offer opportunities for part of the local butterfly population after mowing of a hay meadow, but it appears to be far from a full compensation for the habitat loss induced by cutting. Long-term efficiency of a refuge zone in hay meadows has been shown for orthopterans, but they do not rely on nectar sources .cf. [M. jurtina is protandrous, but in our sample there was much variation in the timing of mowing , but thIn our study areas, refuge zones were relatively narrow, linear elements (width: on average only 3 to 5 m) along the meadow border. It is known from studies on corridors that butterflies fly faster in narrow habitat elements . As popuThe significantly higher frequency of switches between activities most likely relates to lower nectar rewards per flower visit, which in turn demanded higher frequencies of altering between foraging and flying. This likely implies an increase in the physiological cost, as insect flight is energetically costly and particularly so for take-offs . FrequenM. jurtina is known to emigrate from recently cut or grazed areas [Only a low proportion of the tracked females were observed ovipositing. However, our behavioural tracking was not specifically designed to study oviposition in any detail (unlike for example ). We arged areas , and oured areas . ActuallCentaurea jacea is a favourable and preferred nectar source in our sites and this nectar source was visited more often after mowing (based on camera data). This flower species is also frequently visited and highly appreciated by several bee species  [Centaurea genus is fairly continuous throughout the day [Centaurea flowers in the field are always nearly empty, and nectar quantities within the florets were too small to be sampled with a microcapillary  , that wi the day , so evened data; ). Withined data; . Experimed data; ,61. Femaed data; .Our results raise several questions about the optimal quantity and quality of uncut refuge zones in hay meadows for efficient conservation of grassland butterflies and other insects. The location, surface and nectar supply of a refuge zone are key factors in maximizing local resource availability and local survival after mowing. Agri-environmental schemes and management plans often focus on percentages, but the absolute area and shape of the refuge zone should also be considered. Although management techniques to stimulate nectar supply in the refuge zone deserve further attention, a local optimization of the nectar resources within a 5–10% strip of a meadow may not be sufficient for harbouring local populations of nectar-feeding insects. We did not study very small or large refuge zones, but based on our results one could still question the ‘10%-rule’ that is often applied for management regimes with a refuge zone. Our observations of oviposition in the mown zone after mowing suggest that the insect community would benefit from applying several cuts a year, on a fraction of the meadow only, as to finish the season with each fraction having been cut at least once, with uncut zones remaining throughout the year and varying in localization within the site. There is also scope for further work on the effects of local movements induced by mowing. Butterflies move to surrounding landscape elements to find more of the limiting resources (complementation), or other resources absent from the refuge . BesideSparing zones in hay meadows from cutting provides essential resources to grassland arthropods, including flower-visiting grassland butterflies. The principle is well-known and widely applied, but the consequences for local populations in the refuge zones have been largely ignored. We observed a significant increase in butterfly density in the refuge zone after mowing, but not enough to account for total population densities before mowing, indicating a local decline in butterfly abundance. We also showed evidence of changes in behaviour and flower visitation after mowing in line with increased scramble competition for (nectar) resources. Our study raises novel issues about the quantity, configuration and quality of refuge zones in grasslands for animal conservation.


Studies have shown that the presence of attention-deficit hyperactivity disorder (ADHD) causes great impairment in academic, social, and professional activities as well as in the quality of life (QoL) of its patients. Similarly, the impact caused by other chronic disorders, such as diabetes, in the patient’s QoL has been emphasized in many studies. Despite its relevance, no study has yet investigated whether ADHD caregivers and diabetic patients would have similar QoL impairment.This study was conducted in order to compare the QoL scores among ADHD caregivers and diabetic patients.We evaluated 63 caregivers of ADHD children treated at the Child and Adolescent Psychiatric Unit at the Federal University of São Paulo (UPIA-UNIFESP) and 52 adult diabetic patients. Subjects were assessed with the World Health Organization quality of Life-Bref Version (WHOQOL-BREF), the Beck and Hamilton depression scales, and the Adult Self-Report Scale.When compared to the Brazilian normative data, ADHD caregivers had significantly lower scores in the social relations and environment WHOQOL domains. ADHD caregivers and diabetic patients had similar impairment in all WHOQOL domains except for the physical domain.ADHD affects the QoL of the patient’s caregiver, with similar impairment, when compared to the QoL of diabetic patients. These results emphasize the need for assessing QoL of the caregivers as part of the treatment strategies. They also emphasize the need for future studies with larger sample sizes comparing how the QOL is impacted in different chronic disorders. Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent mental disorders in the pediatric population, with prevalence rates ranging from 5 to 7.1% . ADHD coThe concept of QoL has received increased attention over recent years. In general terms, QoL may be thought of as a multidimensional construct incorporating an individual’s subjective perception of physical, emotional, and social well being, including both a cognitive (satisfaction) and an emotional component (happiness) . AlthougDiabetes is a chronic disease considered as a serious public health problem. It is one of the most common chronic diseases worldwide, and its prevalence continues to increase mainly due to the changes in lifestyles resulting in physical inactivity and obesity. It was estimated that diabetes affected 285 million adults between 20 and 79 years in 2010 and will increase to 439 million adults by 2030 .Diabetes affects a patient’s general health and well being in various ways, such as increasing the incidence of weight gain, functional disability, and mortality. Several studies have demonstrated that diabetes also causes a strong negative impact on the patient’s QoL , 15–20. de Ornelas Maia et al.  found thSome studies have also demonstrated the association between the presence of chronic mental and physical disorders and QoL impairment , 22–26. Similarly, some studies have also demonstrated that the QoL is also affected in caregivers of ADHD patients. Cussen et al.  evaluateIn summary, many studies have demonstrated that QoL may be impaired due to the presence of physical , 16, 20 Trying to address this question, this study was designed. The main hypotheses of the study were (1) both caregivers of ADHD children and diabetic patients will have significantly lower scores in all QoL domains, when compared to the general Brazilian population and (2) caregivers of ADHD children would have similar impairments in all QoL domains according to the WHOQOL-BREF when compared to diabetic patients. If proven true, the results would emphasize the need of assessing the QoL of ADHD caregivers, and the need for providing adequate treatment for them.This study consisted of a cross-sectional assessment of two samples. The first one comprised 63 adult caregivers of ADHD children diagnosed according to the DSM-IV criteria, who were being treated at the Child and Adolescent Psychiatry Unit (UPIA) at the Psychiatry Department of the Federal University of São Paulo (UNIFESP). The only inclusion criterion was to be a main caregiver or a child/adolescent with ADHD. The second sample was composed of 52 adults with Type 1 and/or Type 2 diabetes assessed in a reference center of cardiovascular diseases. The inclusion criteria were: having chronic diabetes (having the diagnosis for at least 4 years), not having any previous use of antidepressant drugs, not having a diagnosis of dementia, and not being treated for any psychiatric disorders. We also used the Brazilian normative data for comparisons between the two samples .Data were collected after the approval of the Ethics Committee (IRB) of both sites according to the requirements of Resolution 196/96 of the National Health Council. After a detailed description of the study to all subjects, and the assurance that their decision to participate in the study would not interfere with their access to treatment, all subjects were asked to sign informed consent forms, authorizing their participation in the study.The shortened version, validated to the Brazilian population , 34, useThe Adult Self-Report Scale (ASRS) validated to the Brazilian population has 18 items that assess the presence and frequency of inattention, hyperactivity, and impulsivity symptoms according to the DSM-IV criterion A for ADHD diagnosis. It was used to assess ADHD symptoms in the caregivers of patients with ADHD. The scores range from 0 to 72 points .The Hamilton depression scale (HAM-D) is a well-known scale used to assess the presence and severity of depressive symptoms. It has 17 items, each ranging from 0 up to 2 or 4. The total score can range from 0 (no symptoms) to 52 (very severe) .The Beck depression inventory (BDI) developed to assess presence and severity of depressive symptoms. This scale has excellent psychometric properties and has been validated for the Brazilian population. It contains 21 questions, each ranging from 0 to 3, with total scores ranging from 0 (no depressive symptoms) to 63 (very severe depressive symptoms) –39.Socio demographic data were described as means, SD, and/or percentages, when applicable. Results provided by the WHOQOL-BREF were converted to scores, ranging from 0 to 100. Since the WHOQOL scores did not have a normal distribution, the non-parametric Mann–Witney test was used for the comparisons between each of the two case groups (ADHD caregivers and diabetes) and the Brazilian normative data. We compared each of the groups with the age-matched normative data according to the age ranges described by Cruz et al. .The associations between depression, self-reported ADHD symptoms, and WHOQOL scores were analyzed using bivariate correlations (Pearson’s or Spearman’s when indicated). Since some authors suggest that depression generates impact in QoL , 17, 40 p < 0.05 was used to evince statistical significance. All statistical analyses were performed using SPSS v.16 software for Windows package.A probability level of Among the ADHD caregivers, there were 53 females 84.1%) and 10 males (15.9%). The diabetics group was composed of 34 females (65.4%) and 18 males (34.6%). There were no significant differences between the two groups in terms of gender, years of education, or socioeconomical status. There were significant differences among the groups regarding age (the diabetics group was older). The average age ± SD in the ADHD caregivers was 41.29 ± 10.18 years. In the diabetics, the mean age was 53.55 ± 10.61 years (Table % and 10 p = 0.09), diabetes patients had significantly lower scores in all other three domains when compared to the general population.World health organization quality of Life scores for each of the case groups were compared with the Brazilian normative data Table . Comparip < 0.01). There were no other significant differences between the two groups in the psychological relationships (p = 0.24), social relationships (p = 0.99), or environment domains (p = 0.16).When comparing the four WHOQOL domains between ADHD caregivers and diabetes patients, the diabetics group had significantly lower scores in the physical domain . When considering only the subjects without depression, only the physical WHOQOL domain was significantly different between ADHD caregivers and diabetes patients (p = 0.003). The other WHOQOL domains did not present significant differences between the non-depressed ADHD and Diabetes groups.As shown in Table r = −0.414, p = 0.01), psychological , and social relationships  and environment (r = −0.350 p = 0.01) WHOQOL-BREF domains.Significant negative correlations were found between self-reported symptoms of ADHD (according to the ASRS) in the ADHD caregivers group and the physical (This is the first study comparing the QoL scores between ADHD caregivers and the diabetic patients. Even though some studies have suggested that ADHD has an impact not only on the patient but also in the QoL of their caregivers, we wanted to investigate whether this impact would be similar to the one caused by a chronic disease, such as diabetes. As hypothesized, the results demonstrated similar impairments in the psychological and social relations WHOQOL domains, and therefore, emphasize how ADHD can affect the caregivers and the relevance of addressing this issue with them during treatment , 27.When compared to the general population data, ADHD caregivers had even better scores than the general Brazilian population in the physical domain. On the contrary, diabetic patients had lower scores in the physical domain. It is possible to hypothesize that this difference might be secondary to the fact that ADHD caregivers were younger. This difference is expected since the onset of diabetes is more common after the age of 40 years , while AThe higher impact of diabetes in the WHOQOL physical domain was probably secondary to the frequent limitations in their daily activities –44. de SFleck et al. compared patients with clinical illnesses, psychiatric patients, and normal controls and found that the presence of a psychiatric disorder increased the risk for lower WHOQOL scores on the psychological relationship, social relationship, and environment domains . On the Even though more recent studies have emphasized the impact of ADHD in the caregiver’s QoL, so far, there are only five studies published in the literature investigating QoL in ADHD caregivers , 30–32. In the current study, diabetic patients and ADHD caregivers presented similar impairment on the WHOQOL psychological and social relation domains. Even though this is the first study to compare the WHOQOL scores between these two groups, previous studies have reported that the presence of an ADHD child results in increased likelihood of disruptions in the family and the level of stress and burden in parents , 43. ForIn the current study, the presence of depressive symptoms did not change the impact on the psychological and social relations WHOQOL domains. On the contrary, the physical and environmental WHOQOL domains were significantly worse in the depressed diabetic group.We found significant negative correlations between the ADHD caregivers WHOQOL scores and the severity of ADHD symptoms in the caregivers. Some studies have reported that adults with ADHD usually fail to fulfill their responsibilities, resulting in academic, occupational underachievement, interpersonal problems, emotional difficulties, and other psychiatric comorbidities, such as depression, and most probably affecting their capacity to take care of a child with ADHD . AltogetIt is important to mention the limitations of the current study, such as the small sample sizes, what may limit the generalization of the results. Furthermore, the significant age differences between the two groups and the fact that we did not analyze the impact of the child’s ADHD symptom severity on the QoL of their caregivers are also worth mentioning. A recent study has reported that the child’s levels of attention and opposition symptoms had a significant interference in the psychological and environment domains of maternal QoL .Despite these limitations, the current results reinforce the idea that ADHD impacts the whole family, and that being a caregiver of an ADHD child has an impact on their QoL similar to the one caused by having a chronic disease. They also emphasize the need for future studies with larger sample sizes comparing how the QoL is impacted in different chronic disorders. The results also support the relevance of involving all family members on the treatment strategies for ADHD treatment in order to improve results and promote positive outcomes. The present findings also suggest a need to improve the awareness of health professionals to identify high-risk ADHD caregivers for depression, ADHD and/or other disorders, and refer them as early as possible for treatment.All authors participated in the conceptualization of the research, data collection, data analysis, paper writing, and paper critical review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Bartonella represents a congenial example of the synergistic benefits that can arise from such combined approaches: Bartonella spp. infect a broad variety of animals, are linked with a constantly increasing number of human diseases and are transmitted via arthropod vectors. As a result, the genus Bartonella is predestined to play a pivotal role in establishing a One Health concept combining veterinary and human medicine.Infectious diseases remain a remarkable health threat for humans and animals. In the past, the epidemiology, etiology and pathology of infectious agents affecting humans and animals have mostly been investigated in separate studies. However, it is evident, that combined approaches are needed to understand geographical distribution, transmission and infection biology of “zoonotic agents”. The genus  In the past, health issues played only a minor part in such international economic summits. However, governments have now realized that public health is an essential prerequisite for education, working capacity and therefore the economic prosperity of societies.The threat of infectious diseases to mankind has never been greater than today. For the first time, political leaders of the 41In this regard, it is important to recognize that human health and animal health are closely linked. An estimated 75 % of emerging infectious diseases are zoonotic and 28 % vector-borne . Global Bartonella represents a prototypical example for zoonotic pathogens as Bartonella species are infectious agents for humans and animals. High pathogen prevalence and severe courses of infection raise the importance to investigate possible routes of transmission and to combat infections.To respond to these challenges, the One Health concept aims to establish interdisciplinary collaborations between medical, veterinary and environmental researchers as well as public health officials for the early detection of health hazards affecting both humans and animals and to fight them on multiple levels. The genus Bartonella is comprised of Gram-negative, slow growing and facultative intracellular pathogens that infect mainly mammalian hosts and are often transferred via blood sucking arthropod vectors. Bartonella infections of humans and animals are often characterized by an intraerythrocytic bacteremia. At least 20 species are known to cause host-specific intraerythrocytic infections in their specific mammalian reservoir hosts, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis, the agents of trench fever and Oroya fever, respectively. A secondary tissue phase can be associated with development of vasculoproliferative lesions, e.g. bacillary angiomatosis  or verruga peruana (B. bacilliformis) and may play a role in various other dermal conditions [The bacterial genus of nditions –7.Bartonella. A wide variety of Bartonella spp. specialized to various mammalian hosts and transferred by specific arthropod vectors have been identified over the years and the prevalence of infection appears to be widespread across species and geographic regions. At least 13 species of Bartonella have been identified as pathogenic to humans with three species responsible for most of the clinically relevant infections in humans: B. bacilliformis, B. quintana and B. henselae [Molecular epidemiology techniques have revealed a remarkable diversity within the genus henselae .Bartonella spp. infections are often chronic or asymptomatic in their reservoir hosts. Bacteria have been shown to infect erythrocytes, endothelial cells, macrophages and even human stem cells [Bartonella spp. to persist within immunoprivileged intracellular habitats is probably a key factor contributing to the establishment of chronic infections; however, the cyclic release of bacteria to the blood stream or the hemolytic activity of some species can also result in dramatic illnesses such as trench fever or Oroya fever, respectively [Bartonella spp. in the blood stream of infected hosts or within the erythrocytes also facilitates their transfer via ingestion along with the blood meal of arthropod vectors [em cells –17. The em cells . Localizem cells , 12, 19.ectively . The pre vectors , 21.B. henselae, B. clarridgeiae (both of which can cause cat scratch disease) and B. koehlerae (a causative agent of endocarditis in humans) [Bartonella species are not uncommon [Cats are the main reservoir host for the species  humans) –24. Infe humans) . Co-infeuncommon –29.Bartonella spp. among cats occurs via arthropod vectors, predominantly fleas. Uninfected cats kept together with infected cats in a specific ectoparasite-free environment do not become seropositive emphasizing the importance of arthropod vectors in the transmission of disease. Furthermore, the transmission via arthropod vectors appears to be essential as no direct transmission of B. henselae from cat to cat has been documented experimentally and flea-prevention measures have been shown to be effective in preventing pathogen transmission [versus 68 % in the Phillipines) [Bartonella infections [B. henselae seroreactivity and 50 % were shown to be positive. It is known, however, that serum antibodies have a limited value for the detection of active infections. In the same study, DNA of Bartonella spp. was detected in 4.4 % of the examined cat fleas [Bartonella spp. have also been isolated from cat blood in various other locations throughout the world  [Transmission of smission –35. Prevlipines) , 36–38. fections , 28. Usufections , 23. Catat fleas . BartoneGermany) –49.Bartonella strains which have been isolated from healthy cats were usually not of the same genetic background as those strains detected from infected humans. Some of the feline strains were never found on patients and therefore might be less pathogenic for humans [Those r humans , 51.B. henselae and B. clarridgeiae for months or even years, there is evidence that cats may also suffer from the persistent infection [Bartonella spp. that are not believed to be specifically adapted to the cat as reservoir host (e.g. Bartonella vinsonii subsp. berkhoffii) can result in more serious clinical symptoms, e.g. osteomyelitis [Bartonella spp. but not with seroreactivity and revealed no association with uveitis, neurological symptoms and chronic kidney diseases; however, a weak association between seroreactivity and idiopathic feline lower urinary tract disease was detected [B. henselae or B. clarridgeiae were found to suffer from fever, eosinophilia, lymphadenomegaly and anemia. Perinatal transmission was not described but reproductive disorders were observed. Furthermore, some cats suffered from transient neurological disorders, endocarditis and focal myocarditis [Although healthy cats can be infected with nfection . Especiamyelitis , 31, 52.myelitis , 53–55. detected . Cats excarditis , 57–62.Bartonella spp. has been possible from cats whose owners suffered from cat scratch disease and bacillary angiomatosis and B. clarridgeiae was isolated from a kitten that had caused cat scratch disease in a veterinarian [Bartonella quintana was found in the mouth of a domestic cat and there are reported cases of humans suffering from B. quintana infections where no louse infestation was verifiable but contact with cats was reported [B. qintana was detected in a woman and two cats, one of which had bitten the woman previously providing further evidence for the incidental zoonotic transmission of Bartonella between animals and humans [Bartonella prevalence in cats and therefore reduces the risk of pathogen-transmission to humans [Isolation of rinarian , 40, 63.reported , 64. In d humans . Antimico humans , 35.Bartonella and two species are known to cause clinically apparent infections: B. vinsonii subsp. berkhoffii, causing endocarditis, arrhythmias, myocarditis, granulomatous lymphadenitis and granulomatous rhinitis, and B. henselae causing peliosis hepatis [Bartonella bacteremia in dogs, B. henselae was found in 30 of 61 infected dogs [Bartonella spp. have caused disease in dogs: B. clarridgeiae, B. washoensis and B. quintana were isolated from dogs suffering from endocarditis [Bartonella spp. identified in sick dogs are also known as pathogenic or potentially pathogenic infectious agents for humans and this observation led to the suggestion that dogs might act as useful sentinel species and important comparative models for human infections [Dogs represent an incidental host for  hepatis –71. In ated dogs ; howevercarditis , 22, 23.fections .B. henselae with a reported seroprevalence of ~10 % in healthy dogs in the United States and ~27 % in sick dogs [Bartonella henselae, B. quintana, B. vinsonii subsp. berkhoffii and B. bovis have been detected in mouth swabs from dogs and there is some evidence that dogs may be able to transmit B. henselae to humans via bites [B. vinsonii subsp. berkoffii in dogs, they are suspected to represent the reservoir host of these bacteria and seroreactivity of dogs against B. vinsonii subsp. berkoffii is found worldwide [B. clarridgeiae was also isolated from ~2 % of the examined dogs indicating that these animals may represent a potential reservoir host for Bartonella spp. in Africa [Domestic dogs are generally incidental hosts for ick dogs , 74. Simick dogs . Bartoneia bites , 37, 75.orldwide , 26, 32.n Africa .B. vinsonii subsp. berkhoffii may also cause immuno-mediated hemolytic anemia, neutrophil or granulomatous meningoencephalitis, neutrophil polyarthritis and uveitis in dogs [Bartonella vinsonii subsp. berkhoffii can cause endocarditis, especially in large breed dogs with a predisposition for aortic valve involvement. Intermittent lameness and fever of unknown origin can occur several months before endocarditis. Myocarditis without an associated endocarditis is also possible and may result in arrhythmias, syncope or sudden death [Bartonella spp. as the causative agent of infectious endocarditis in dogs, diagnostic PCRs should be performed from blood or heart valve specimen as blood cultures often remain negative [Bartonella endocarditis. In most cases, Bartonella infect the aortic valve causing aortic insufficiency leading to severe chronic heart failure and arrhythmias [Serological surveys suggest that  in dogs , 22. Baren death , 67. To negative , 78. Highythmias , 79, 80.Bartonella infections of numerous mammals and even reptiles. For instance, Bartonella spp. have been detected in a wide variety of wild and domestic animals throughout the world including, e.g. mountain lions, bobcats, coyotes, grey foxes, elks, mule deer, cougars, rabbits, several rodent species, cattle, belugas, bats and porpoises. However, it is unclear which diseases if any are associated with such infections and if these animals play a role as potential reservoir hosts. [There are many publications describing r hosts. , 81–92.Bartonella species to be identified in the early 1900s was B. bacilliformis. This human-specific bacterium causes a biphasic disease characterised by a primary hemolytic fever (“Oroya fever”) with high mortality (up to 90 %), followed by a chronic vasculoproliferative tissue phase (“verruga peruana”). Pathogens are transmitted by the sand fly (Lutzomyia verrucarum). The human body louse (Pediculus humanus humanus) transmits B. quintana, a second human pathogenic Bartonella species which emerged as a major agent of disease causing debilitating cyclic fever (“trench fever“) during World War I. Today, trench fever occurs mainly in the homeless population or among drug addicts. Endocarditis, generalized lymphadenopathy and bacillary angiomatosis are symptoms of B. quintana infections in immunocompromised people [The first human pathogenic d people –100.Bartonella species B. henselae is the most common symptomatic infection causing agent identified in the modern clinical setting. Bartonella henselae infection is the cause of multiple clinical entities in humans and infections result in differential disease outcomes often depending on the immune status of the patient. Humans become infected via the scratches or bites of infected cats contaminated with infected flea feces or are directly contaminated with infected blood. Dogs are also suspected to be an additional reservoir for B. henselae transmission to humans [Of the three most significant human pathogenic o humans . In immuo humans . Recurrio humans , 19.Bartonella spp. have been reported as cause of fever of unknown origin and culture-negative endocarditis in humans and animals [B. henselae, B. quintana, B. elizabethae, B. vinsonii subsp. berkhoffii, B. vinsonii subsp. arupensis, B. koehlerae, B. alsatica, B. washoensis and Candidatus B. mayotimonensis have been reported [B. henselae and B. quintana [Bartonella-IgG antibody-titers can be detected [Several  animals –105. In reported , 106–114quintana , 80, 115detected , 116.Bartonella spp. (even in immunocompetent patients) [Borrelia burgdorferi (sensu lato) and B. henselae were described in patients with atypical neuroborreliosis [B. henselae in people suffering from persistent symptoms after borreliosis treatment where ticks might have been the source of infection [Bartonella and Borrelia co-infections, laboratory diagnostics were not properly performed [Co-infections with more than one atients) –119 and reliosis –122. Furnfection . The tranfection , 124. Hoerformed .Bartonella spp. [B. vinsonii subsp. berkhoffii, transmission to a veterinarian was likely caused by a needle puncture injury [Bartonella infections have even been suspected to have been a contributing factor in the death of two veterinarians in 2013 [Bartonella DNA was also detected in the blood of 28 % of veterinary workers whereas no Bartonella was detected in control subjects [Bartonella infections has also been found to be elevated in other risk groups. In a recent study in Germany B. henselae IgG antibodies were found in ~45 % of forestry workers which may be due to a higher contact with arthropods which is inevitable during forest work [Bartonella transmission is crucial to reduce occupational hazards in certain risk groups and prevent such cases of Bartonella transmission in future.Different population groups are exposed to animals and arthropod vectors in variable dimensions. In particular, veterinarians, veterinary technicians or zookeepers might be at increased risk of infection with lla spp. , 126. Foe injury . Bartone in 2013 . In an eest work . From a Bartonella infections. The transmission of infection via blood transfusion was first shown 20 years ago in cats [Bartonella spp. in asymptomatic human blood donors. Remarkably, the results of this study found that professionals with animal contact were seven times more likely to harbor Bartonella than other blood donors and individuals with cat contact or a history of tick bite were three to four times more likely to be infected with Bartonella spp. [Bartonella infections, especially in certain risk groups should be considered to prevent transmission of infection.Blood transfusion has also been identified as a risk factor for the transmission of  in cats  and a vella spp. . ConsideBartonella spp. transmission and additional vectors competencies are suspected in many more.The transmission cycle of bartonellosis is typical for vector-borne diseases. Typically, infections are characterized by persistent intraerythrocytic bacteremia within the reservoir host. Infected blood is ingested by the blood sucking arthropod vector and subsequently transmitted to a further reservoir or incidental host. To date, vector-competence of several arthropods has been proven for Ctenocephalides felis) represents the main vector for B. henselae infection among cats. Its vector-competence for B. henselae transmission is experimentally proven and its presence is essential for the maintenance of B. henselae infection within the cat population. The contamination of the flea-feeding wound, or other wounds such as scratches or bites with contaminated flea feces has been identified as an important transmission route among hosts including cats and humans [B. henselae within 24 h of a blood meal [The cat flea  represents the vector of human to human-transmission of B. quintana. Environmental factors supporting louse infestation such as unhygienic living conditions lead to an increased risk of infection. In the past, infections with B. quintana were a severe medical problem in the trenches and in prisoners of war camps of World War I from which the name “trench fever” arises. Today, mostly homeless people or drug addicts are affected resulting in the term “urban trench fever” [Bartonella quintana reaches the louse gut and can infect humans when bite sites or other wounds are contaminated with infected louse feces [Bartonella spp. have also been detected from several other louse species  which may also serve as vectors [The human body louse  transmits B. bacilliformis from humans to humans and its vector-competence has been proven experimentally [B. bacilliformis.The sand fly  usually feed three times during their life-cycle and can possibly be infected with different pathogens during every blood meal. Hosts can be bitten by ticks several times during their lifetime presenting multiple opportunities for pathogen transmission [Bartonella spp. in various tick species from around the world [Bartonella DNA in hard ticks in Europe has been shown to be as high as 40 % [Bartonella DNA whereas DNA of Borrelia spp. was found frequently at ~ 19 % [Bartonella DNA was detected in ~2 % of ticks collected in a recent study from Austria [Bartonella in different studies. Overall, in ~15 % of ticks studied Bartonella DNA was detectable.Ticks are known to act as vectors for many different bacterial, protozoan and viral pathogens. Hard ticks  in dogs [Bartonella were also seroreactive to Anaplasma phagocytophilum, another tick-borne pathogen [eviously . Further in dogs , 174–178pathogen .B. henselae DNA was detected in ticks collected from the home of patients which suffered from Lyme disease and which did not respond to a Borrelia-specific antibiotic therapy. In another study, Bartonella DNA was detectable in human blood after tick bites and recently, B. henselae and three other animal-associated Bartonella species  were isolated from patients suffering from undifferentiated chronic illness and who had reported tick bites [In two cases, ck bites , 180.B. henselae infections of humans have been published where no or very limited cat contact was reported, limiting the possibility of transmission via cats or cat fleas. Authors concluded that transmission via arthropod vectors (e.g. ticks) may provide an alternative explanation [Several case reports of lanation , 181.Bartonella spp. have been detected in these small mammals further supporting the possibility that ticks may represent a vector for Bartonella transmission [Bartonella spp. have also been isolated from cattle and mule deer in North America. As ruminants are rarely infested with fleas, ticks seem to be more likely to transmit these pathogens to these animals [The most important reservoir hosts for tick-borne pathogens are small rodents as they are the preferred hosts of tick larvae and nymphs. Several smission , 183. Ba animals .Bartonella spp. via ticks to humans and animals is still controversially discussed. Clearly, Bartonella DNA which was found in several tick species in multiple studies does not prove the presence of viable bacteria. Therefore, some researchers doubt heavily that Bartonella spp. are transmitted by ticks [B. henselae strain that was used is not representative for Bartonella strains found in nature [Bartonella spp. from ticks to mammalian hosts [B. birtlesii, tick transmission was proven in a murine infection model [bona fide tick transmission of B. henselae has not been demonstrated so far.Nevertheless, it must be mentioned that the transmission of by ticks , 184. Fuby ticks  have beean hosts . At leason model  whereas Bartonella species have been found in biting flies collected from cattle in California: B. bovis was detected in a horn fly (Haematobia spp.) and B. henselae was found in a stable fly (Stomoxy spp.) [Bartonella spp. in mites collected from rodents and bats from Korea, Egypt and Costa Rica [Lipoptena mazamae and Lipoptena cervi) were shown to be infected with B. henselae and B. schoenbuchensis [Lipoptena species usually feed on deer but were also found on horses, cattle and humans. Bartonella schoenbuchensis was detected in Lipoptena cervi from a deer (Capreolus capreolus) in Germany and is suspected to be the causative agent of deer ked dermatitis in humans [Bartonella was also found in several other species of the family Hippoboscidae indicating that they may play a role in the transmission of these bacteria [B. schoenbuchensis by Lipoptena spp. to humans.xy spp.) . Severalsta Rica , 186. Deuchensis , 187–189n humans . Bartonebacteria , 191. HoBartonella spp. from animals to humans, e.g. via arthropod vectors, a more integrative approach elucidating Bartonella prevalence in vectors as well as the infection status of animals and humans would clearly help to increase understanding of Bartonella infection dynamics, infection risk and prevent speculative and non-evidence-based conclusions. Such an approach might, for instance, include the investigation of the prevalence of Bartonella DNA or (even more reliable) of viable Bartonella species in feeding ticks, combined with parallel detection of these pathogens via direct detection or seroprevalence in animals (e.g. pets) and humans (e.g. pet owners). Figure When discussing transmission of Bartonella 16S-rDNA sequences; analyzed by conventional PCRs or metagenomics analysis), (ii) the direct detection of these pathogen(s) or detection of pathogen-specific (e.g. Bartonella) antibodies in animals (arguing for infection of the pet), and (iii) the direct detection of these pathogen(s) if feasible or the determination of the respective pathogen-specific antibodies in humans (e.g. pet owner) in parallel (arguing for a previous or present infection).For instance, a coordinated set of data might include (i) the pathogen-DNA status of questing ticks  which was feeding for ~1–2 days on a cat, Bartonella-DNA was detected via nested-PCR. Sequence analysis revealed most likely the presence of B. henselae 16S-rDNA (99 % sequence homology). For medical reasons, a serum sample from the cat was taken (because of unspecific illness). Immunofluorescence testing revealed cat antibody titers of 1:640 whereas no specific B. henselae-antibodies were detected in the pet owner. This setting might be interpreted as follows: The questing I. ricinus tick was probably ingesting B. henselae-containing cat blood as anti-B. henselae IgG antibodies were detectable. The pet owner, however, had no serological evidence for having been exposed to B. henselae. As a further option, a chronic B. henselae infection of the cat might additionally be confirmed . The application of such One Health approaches in prospective scientific studies would be useful to assess the real risk of transmission of Bartonella spp. from pets to pet owners and to clarify the role of ticks in this process.First incidental results from a clinical case revealed interesting findings: In a female, adult, half-engorged Bartonella spp. might represent an underappreciated danger for human and animal health. A great deal more research is needed to specify arthropod vectors and characteristics of diseases caused by Bartonella species. To date, strict ectoparasite-control is highly recommended to lower the risk of Bartonella infection from arthropod vectors to domestic animals and pets, thereby preventing pathogen transmission from animals to human owners. Overall, these results demonstrate that reliable data about vector transmission of Bartonella spp. from animals to humans can only be generated through the application of scientific One Health approaches which take into account the epidemiological factors and interactions of humans, animals and their environments as an integrated system.The cumulative data collected in many studies and conducted in several countries throughout the world indicate that infections with


Deficient cognitive top-down executive control has long been hypothesized to underlie inattention and impulsivity in attention-deficit/hyperactivity disorder (ADHD). However, top-down cognitive dysfunction explains a modest proportion of the ADHD phenotype whereas the salience of emotional dysregulation is being noted increasingly. Together, these two types of dysfunction have the potential to account for more of the phenotypic variance in patients diagnosed with ADHD. We develop this idea and suggest that top-down dysregulation constitutes a gradient extending from mostly non-emotional top-down control processes  to mainly emotional regulatory processes (including “hot” executive functions). While ADHD has been classically linked primarily to the former, conditions involving emotional instability such as borderline and antisocial personality disorder are closer to the other. In this model, emotional subtypes of ADHD are located at intermediate levels of this gradient. Neuroanatomically, gradations in “cool” processing appear to be related to prefrontal dysfunction involving dorsolateral prefrontal cortex (dlPFC) and caudal anterior cingulate cortex (cACC), while “hot” processing entails orbitofrontal cortex and rostral anterior cingulate cortex (rACC). A similar distinction between systems related to non-emotional and emotional processing appears to hold for the basal ganglia (BG) and the neuromodulatory effects of the dopamine system. Overall we suggest that these two systems could be divided according to whether they process non-emotional information related to the exteroceptive environment (associated with “cool” regulatory circuits) or emotional information related to the interoceptive environment (associated with “hot” regulatory circuits). We propose that this framework can integrate ADHD, emotional traits in ADHD, borderline and antisocial personality disorder into a related cluster of mental conditions. Arguably, altered regulation of information processing represents the core underlying mechanism for many psychiatric disorders. Such aberrations can affect multiple dimensions, including both non-emotional and emotional processes. Currently, some disorders are conceptualized as dysfunction of one or the other of these dimensions. For example, attention-deficit/hyperactivity disorder (ADHD) is defined on the basis of dysfunctional regulation of non-emotional information processing , whereas disorders such as borderline personality disorder (BPD), antisocial personality disorder (ASPD) and conduct disorder (CD) entail symptoms reflecting emotional instability associated with dysfunctional regulation of emotional processes. Other disorders involving emotional instability include intermittent explosive disorder and oppositional defiant disorder (ODD). Traditionally, these psychiatric disorders have been studied separately, reflecting their historical categorical divisions, and the tendency of investigators and disciplines to reify such distinctions. However, these historical distinctions are increasingly appreciated as having impeded understanding of specific disorders in relation to each other. In this Hypothesis and Theory article, we propose that dysregulation in these different dimensions can be incorporated into a unified model.Although disorders that include persistent emotional dysregulation differ in many symptoms, recent neurocognitive research results suggests common features are involved in emotional dysfunction. These “emotional instability disorders” are characterized by emotional hyper-responsiveness in amygdala and insula, regions involved in shaping emotional responses and experience Blair, . StructuSeveral reviews and theoretical articles have recently discussed how top-down regulation in ADHD differs in comparison to specific emotional instability disorders including BPD . Given that the disorders are mechanistically related we also hypothesize that the symptoms associated to one type of dysregulation will be overly represented in patients that have the disorder associated with the other type of dysregulation—even when there is no explicit comorbidity (Hypothesis 2). Thus, a dimensional approach would better describe the existing phenotypes than categorical distinctions. Finally, if the underlying mechanisms are similar, treatments proven to be efficacious for one category of disorders should also be efficacious for the other category of disorders (Hypothesis 3). This could open new important possibilities for treatment.In more detail, we will put forward a model in which ADHD and emotional instability disorders are mechanistically related. We will argue that the fundamental problem in both types of disorders is a similar dysfunctional top-down regulation of information processing, in which the difference between the two types of categorical disorders  is whether the dysfunctional top-down regulation is associated with emotional (and interoceptive) processing or non-emotional (and exteroceptive) processing  and ADHD. Given that executive functions are fundamentally associated with ADHD, we then review the underlying prefrontal networks in the brain mediating such top-down control and show that these systems are altered in ADHD. A similar review will be done for emotion associated (“hot”) executive functions and emotional regulation, and their relation to emotional instability disorders as well as for “emotional” traits in ADHD. We then discuss how systems mediating emotional and non-emotional top-down regulation (and dysregulation) relate to each other in prefrontal, striatal and dopamine networks. We will also discuss how this stratification between emotional and non-emotional regulation could be discussed in terms of systems related to interoceptive and exteroceptive processing. Finally, we present a model that can incorporate both ADHD and emotional instability disorders based on the relationship between these top-down regulatory systems.fundamental behavioral components that may be altered in multiple psychiatric disorders, such as attention or emotional regulation as a part of the Research Domain Criteria (RDoC) initiated by the USA National Institute of Mental Health  and attention  in task-based studies /vlPFC . However, a range of other studies suggests a general role for the ACC in emotional regulation. Importantly, although the rACC and cACC differ in their involvement in attentional tasks—as has long been suggested , an area neighboring rACC, supports extinction while cACC supports increased aversive processing  suggest that rACC and neighboring vmPFC are specifically involved in emotional regulation of lower-level structures including amygdala, PAG and ventral striatum. This effect seems to be specific for emotion/pain processes and supports the idea of a system sub-specialized for “hot” executive functions and emotional regulation.Above we have suggested that OFC has an important role in explicit emotional regulation such as cognitive re-appraisal, in which subjects are asked to modulate the emotions associated with a picture (see above). How does this relate to the general function of OFC? The OFC comprises a complex set of regions that may be differentiated along medial-lateral and anterior-posterior gradients  that drive behavior  as indicated by meta-analysis  it may be questioned whether these regions also differ in structure and function in conditions characterized by emotional instability.Several studies of brain morphometry have been conducted in emotional instability disorders including BPD, ASPD and CD. Although, they represent initial steps in understanding the underlying pathophysiology, there are two major problems with many of these studies. The first is that most studies have been underpowered, with few patients and controls. The second is that ADHD has not been considered. Nevertheless, two relatively well-powered volumetric studies of BPD  between amygdala and rACC and between amygdala and posterior insula were significantly correlated with parent ratings of emotional dysregulation in children with ADHD  nor an increased risk to have dysregulation in another dimension as compared to healthy subjects. However, this is not the case. The comorbidity between ADHD and the different emotional instability disorders is remarkably large. For example, 42% comorbidity between ADHD and BPD was reported in adolescence and 16% in adulthood in a BPD sample  has been studied as a neurocognitive endophenotype marker across disorders  and the other regressor quantified non-emotional ADHD traits , which in turn can provide interoceptive feedback to “hot” circuits James, , 2009. TWhile it is not clear to what extent early interoceptive signals are prone to modulation, it has been shown that all parts of insula  as well as cACC may be regulated by top-down systems during processing of bottom-up interoceptive input  suggests a demand for two different regulatory functions as well. One proposal would be that cACC and dlPFC regulate processes related to the exteroceptive world, while rACC and lOFC regulate processes related to the interoceptive world and its needs by controlling information processing in insula, cACC, amygdala, ventral striatum and the brainstem. As every individual acts in an external environment, these networks need to interact at multiple levels. The division between interoceptive and exteroceptive networks, including their specific top-down regulatory systems, fits with the observation that some individuals have problems that relate more to a specific dimension of top-down control such as “non-emotional” regulation or “emotional” regulation. A testable hypothesis derived from this reasoning is whether processing of more classical interoceptive input is also dysregulated in subjects with emotional instability.Hypothesis 1).We have presented a model in which ADHD and emotional instability disorders  are mechanistically related in that they all involve similar dysfunctional top-down regulation of information processing. We hypothesized that the difference between the classically defined disorders  is whether this dysfunctional regulation is related to emotional (and interoceptively associated) processing or non-emotional (and exteroceptively associated) processing . Therefore, a dimensional approach should better describe the problems of most patients. In the present article we have highlighted research suggesting that top-down regulatory capacities of the emotional and the non-emotional systems vary in their efficiency among subjects in the general population . This idea is in line with initial studies, suggesting that methylphenidate also has an impact on emotional dysregulation behaviors in ASPD and CD  and “Projektmedel för forskning och utveckling inom psykiatri, primärvård och geriatrik, PPG” (20140301). FXC was partially supported by NIH grant U01MH099059.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The effect of hexadecyltrimethylammonium bromide (CTAB), triton X-100 (TX100) and 4-dodecylbenzenesulfonic acid (SDBS) was tested. The Daphtoxkit F™ test (conforming to OECD Guideline 202 and ISO 6341) was applied for the toxicity testing. Both the surfactants and the ENPs were toxic to D. magna. The addition of ENPs to a solution of the surfactants caused a significant reduction of toxicity of ENPs. The range of reduction of the toxicity of the ENPs depended on the kind of the ENPs and their concentration in the solution, and also on the kind of surfactant. For nano-ZnO the greatest reduction of toxicity was caused by CTAB, while for nano-TiO2 the largest drop of toxicity was observed after the addition of TX100. In the case of nano-Ni, the effect of the surfactants depended on its concentration. Most probably the reduction of toxicity of ENPs in the presence of the surfactants was related with the formation of ENPs aggregates that inhibited the availability of ENPs for D. magna.The objective of the study was the estimation of the effect of surfactants on the toxicity of ZnO, TiO This is indicated by the great increase of their production and application in various areas of life  and non-ionic (Triton X-100) surfactants towards Daphnia magna. It is estimated that among inorganic nanomaterials (apart from Ag) the highest production is characteristic of nano-ZnO and nano-TiO. ZnO and TiO2 NPs are widely used in the consumer products  which needs the detailed assessment of their potential toxicity to different organisms. The growing scale of production of NPs involves the risk of their release into the environment. Ni nanoparticles, on the other hand, are used in production catalysts, battery electrodes and diesel–fuel additives and also may released to environment. While for ZnO and TiO2 there are a lot of data on their toxicity, in the case of Ni NPs data on this subject are limited. Thus, it is important to evaluate the effect of the surfactants on both the common nanoparticles, such as ZnO and TiO2 but also less popular NPs, such as Ni NPs.The objective of the study presented here was the estimation of the toxicity of various ENPs—nano-ZnO, nano-TiO2  and Ni (nano-Ni) were purchased from Sigma-Aldrich (USA). CAS numbers of used metal and metal oxide nanoparticles were: 1314-13-2 (nano-ZnO), 13463-67-7 (nano-TiO2), 7440-02-0 (nano-Ni). The ENPs (the purity was around 99.5 %) were used as powder. The primary particle size of ENPs was as follows: nano-ZnO < 100 nm; nano-TiO2 < 21 nm; nano-Ni < 100 nm. The size of ENPs was determined by transmission electron microscope . Surfactants  were purchased from Sigma-Aldrich (USA). All solutions were prepared using analytical grade reagents and HPLC grade water .Nanoparticles ZnO (nano-ZnO), TiO3, 123.25 mg/L MgSO4 × 7H2O, 294.0 mg/L CaCl2 × 2H2O). In the each steps of experiment, the standard ISO medium without ENPs and surfactants was used as a control.Samples of ENPs as well as surfactants were prepared in the ISO medium for Daphtoxkit F bioassay . The solutions of ENPs and of the ENPs with surfactants were sonicated for 30–minute at temperature of 25 °C in an ultrasound bath  before application on the test plates.D. magna. The whole procedure was carried out according to the user’s manual (Daphtoxkit 2Cr2O7). The quality control test was successful.The Daphtoxkit F™ bioassay  was used to estimate effect of surfactants on the toxicity of ENPs to crustacean . The pH and O2 of samples was measured. The SEM–EDS analyses were conducted to observe nanoparticles on/inside D. magna. The SEM–EDS measurements were made with the high vacuum with accelerating voltage mode. Using the EDS maps it is possible to see Zn, Ti and Ni particles in/on D. magna. The EDS diagrams (below SEM–EDS maps) show spectrums, which present characteristics X-rays of sample atoms induced by electron beam (30 keV). The SEM–EDS maps (with 50-fold magnification) and were obtained for whole organism just after the exposure time. The EDS spectra confirm and correspond with the contribution of elements  in the whole sample area. In this particular case the organisms were taken from the solutions of NPs at concentration of 100 mg/L suspended in: (1) the ISO medium used in the test, (2) SDBS solution , (3) CTAB solution  and (4) TX-100 solution (1 mg/L).The ISO medium with ENPs alone and ENPs with surfactants was characterized using dynamic light scattering (DLS) , transmission electron microscopy (TEM)  and scanninig electron microscopy with energy dispersive spectrometry (SEM–EDS) . For these analysis, the samples were prepared in following way: NPs at concentration of 100 mg/L were suspended in: (1) the ISO medium used in the test, (2) SDBS solution , (3) CTAB solution  and (4) TX-100 solution (1 mg/L) and pontificated for 30 min. The size of aggregates and zeta potential were measured by DLS technique 50 values are the average of three independently replicates. The differences between toxicological data (EC50 for NPs only and NPs with surfactants) were evaluated using the Kruskal–Wallis test followed by post hoc Nemenyi test. Other differences between NPs and NPs with surfactants  were determined using a one-way analysis of variance (ANOVA) followed by Dunnett’s post hoc test.Effect concentrations (EC) were derived from full log-logistic (surfactants) or linear (ENPs) concentration effect curves. The reported ECD. magna. The toxicity was varied with relation to the kind of surfactant applied. A gradual increase in the toxicity of the surfactants was observed with increase in their concentration. CTAB, already at the concentration of 0.05 mg/L, caused 100 % immobility of the test organisms. For SDBS, 100 % immobility was observed only after the concentration of that surfactant reached the level of 0.5 mg/L. The values of EC50 determined for CTAB and SDBS were 0.03 mg/L and 0.12 mg/L, respectively. The toxicity of TX100 towards D. magna was the lowest relative to the two other surfactants. The value of EC50 assayed for TX100 was at the level of 98.7 mg/L and it was higher by over two orders of magnitude compared to that for SDBS and by three relative to CTAB  to 7.3 and a level of O2 was above 3 mg/L. Generally, colloidal suspensions with zeta potential above 20 mV and those more negatively charged than −20 mV are considered stable , and therefore in the range studied we have a positive value of the potential, and the shift of the slipping plane can result in its increase. In this case the aggregation of particles in the system may be affected the phenomenon of flocculation, where there is no decrease of the potential as a result of joining of colloids via hydration layers.ENPs differed from one another in the values of the zeta potential Fig. . In the 2 and nano-Ni caused an increase in the rate of immobility of D. magna  were obtained for nano-ZnO by Zhu et al.  to values at the level of as much as 1.3–3 mg/L , followed by CTAB  and finally SDBS (25–66 %). As opposed to nano-ZnO, greater reduction of toxicity was observed for higher concentrations of nano-TiO2. In addition, even at the highest concentration tested the toxicity of nano-TiO2 in solutions containing the surfactants was significantly lower compared to the solution without any surfactants. The toxicity of nano-Ni was also reduced under the effect of the surfactants, with no significant differences observed among the surfactants for most of the concentrations tested. The reduction of toxicity (from 0.05 to 10 mg/L nano-Ni) varied from 60 to 100 % . Only at the highest concentration tested significant differences were observed among all the surfactants. The best reduction was obtained for TX100 (80 %), followed by SDBS (70 %), and the lowest for CTAB (60 %) for the highest concentration of nano-Ni.The addition of the ENPs to solutions of all the surfactants caused a reduction of their toxicity within the whole range of concentrations applied Fig. . The excnts Fig. b. In theStudies on the effect of surfactants on the toxicity of ENPs are relatively scarce , rather than their core sizes. This finds support in SEM–EDS images , which excludes that factor as a possible one. Das et al. (D. magna direct interactions with the ENPs. Reduction of toxicity undoubtedly results from interactions of ENPs with surfactant particles. Dabrunz et al. (2 sink to the bottom of the test beakers. The addition of surfactants to the solution increases the size of aggregates, as a result of which they become heavier and sediment faster compared to ENPs alone (Chibowski et al. D. magna than when suspended in the solution, but also direct contact of ENPs with D. magna is limited. In addition, the binding of ENPs by surfactants may inhibit the solubility of ZnO and Ni, which—according to certain authors—determines primarily the ecotoxicity of ENPs. That last issue, however, requires additional research.Although a reduction of toxicity after the addition of the surfactants was observed for all ENPs, the hypothesis suggested earlier that the reduction of bioavailability or surface coating reduces the toxicity of ENPs in the presence of surfactants cannot be applied to nano-TiOiO2 Fig. b and naniO2 Fig. c the conity Fig. b in the gna Fig. b. No simgna Fig. c. Analysr et al.  suggestes et al.  suggest z et al.  demonstrThe presence of surfactants considerably reduced the toxicity of all tested ENPs. Although earlier studies showed that surfactants may increase the toxicity of ENPs towards plants, an opposite tendency was observed in this study. This indicates that in the analysis of the toxicity of ENPs it is very important to take into account various groups of organisms, because of different potential mechanisms of ENPs toxicity. Generalization of results may lead to erroneous conclusions. A positive aspect of the results obtained is that the toxicity of ENPs can be reduced as a result of their contact with surfactants, which reduces the risk to the environment. On the other hand, however, surfactants—increasing the aggregation of ENPs—reduce their mobility and that may mean a longer time of retention of those contaminants. These problems assume a growing importance in view of the every greater production of surfactants and ENPs alone. It should also be emphasised that surfactants are used for the stabilisation of ENPs in ecotoxicological studies. That may lead to incorrect estimation of the toxicity of ENPs. Underestimation of the environmental hazard may lead to serious environmental consequences, with potential effect on various groups of organisms.


Low birth weight (LBW) infants do not form a homogeneous group; LBW can be caused by prematurity or poor fetal growth manifesting as small for gestational age (SGA) infants or intrauterine growth retardation. We aimed to clarify the relationship of maternal smoking with both SGA and preterm LBW infants.The study population comprised pregnant women who registered at the Koshu City between January 1, 1995, and December 31, 2000, and their children. We performed multivariate analyses using multiple logistic regression models to clarify the relationship of maternal smoking during pregnancy with the SGA outcome and preterm birth in LBW infants.In this study period, 1,329 pregnant women responded to questionnaires, and infant data were collected from 1,100 mothers (follow-up rate: 82.8%). The number of LBW infants was 81 (7.4%). In this cohort, maternal smoking during early pregnancy was associated with LBW and the SGA outcome. Maternal smoking during early pregnancy was a risk factor for LBW with SGA outcome and for LBW with full-term birth. However, it was not a risk factor for LBW with appropriate weight for gestational age (AGA) and LBW with preterm birth.These results suggested that LBW with AGA and LBW with preterm birth were associated with other risk factors that were not considered in this study, such as periodontal disease. For the prevention of LBW, not only abstinence from smoking during pregnancy but also other methods such as establishing a clinical setting should be adopted. In 1975, 5.5% of all infants born weighed less than 2,500 g, while in 2003, this value increased to 10.1%.3,4 Preterm birth accounts for a large proportion of neonatal deaths.5,6 It is also increasingly recognized that SGA babies have an increased risk of developing chronic diseases in adulthood, such as hypertension, type-2 diabetes, and coronary heart disease.7,8The cause of LBW infants can be either preterm birth or poor fetal growth manifesting as small for gestational age (SGA) infants or intrauterine growth retardation (IUGR). Moreover, LBW, SGA, and prematurity or a combination of these outcomes are closely related to neonatal and long-term morbidity.9-11 It also increases the risk of preterm birth6,9 although it appears to affect fetal growth more than gestational duration.5Maternal smoking during pregnancy is a strong dose-dependent risk factor for LBW.5,9,10,12,13 however, there was an overlap among the outcomes in these studies. LBW infants do not form a homogeneous group. For example, LBW babies who are SGA and those who show appropriate weight for gestational age (AGA) do not exhibit the same characteristics. To our knowledge, the relationship between maternal smoking and LBW has not been studied by classifying LBW infants into SGA and AGA and into preterm and full term. From the viewpoint of clinical and public health, to prevent LBW, it was important to obtain further information regarding maternal smoking during pregnancy as a risk factor for LBW.The relationship between maternal smoking during pregnancy and each of these pregnancy outcomes, namely, LBW, SGA infants, and preterm birth, have been reported in many previous studies;Moreover, no population-based study has been conducted for identifying the difference in the etiologies of SGA and AGA babies and of preterm and full-term birth in LBW infants.This study aimed to clarify the relationship of maternal smoking with LBW by classifying LBW infants into SGA and AGA babies and into preterm and full-term babies by using data from a prospective cohort study in Japan.The study population comprised pregnant women who registered at the city office in Koshu City, Yamanashi Prefecture, Japan, between January 1, 1995, and December 31, 2000, and their children. The subjects were the participants of Project Koshu, a dynamic prospective cohort study consisting of pregnant women and their children in a Japanese rural area. This project commenced in 1988 and continues to date. Koshu City has a population of 27,000 with approximately 200 births occurring each year. We expected a high follow-up rate in this project because most of the people in this city had not migrated elsewhere. In the present study, we used a part of the data obtained from this project.In Japan, pregnant women must register at a city office, and after delivery, the children must be registered by their parents. First, when the expectant mothers visited the city office for pregnancy registration, a questionnaire-based survey was conducted to ascertain their lifestyle habits, after obtaining informed consent. Over 95% of the expectant mothers in Koshu City registered before week 16 of pregnancy. Next, during their children’s medical checkup at a public health center, we obtained data regarding the gestational age at birth and birth weight that were recorded in the Maternal and Child Health Handbook by the obstetrician or midwife in charge of delivery.In order to ensure confidentiality, the mothers and children were identified using unique numbers; these numbers were used to match the data obtained from the earlier pregnancy survey and those obtained at the children’s medical checkup performed when they reached 5 years of age.We obtained informed consent from the participants of Project Koshu. This study was approved by the Ethical Review Board, Yamanashi University School of Medicine, based on the “Guidelines Concerning Epidemiological Research”  and was performed in cooperation with the Koshu City administration office.2)).The lifestyle immediately before pregnancy and during early pregnancy, including the smoking status during early pregnancy, was assessed based on a self-reported questionnaire administered at pregnancy registration. In this study, we used the following items as independent variables: sex of the child, birth order of the children, gestational age (weeks) at delivery, maternal age, maternal height, maternal body mass index (BMI) in the non-pregnant state, occupational status, smoking habits during early pregnancy, alcohol consumption during early pregnancy, breakfast habits, gestational age (weeks) at pregnancy registration, and maternal attitude toward pregnancy when the pregnancy was confirmed. Maternal body height and weight in the non-pregnant state were obtained from the data recorded in the Maternal and Child Health Handbook by the attending obstetrician or midwife. Maternal BMI was calculated according to World Health Organization standards (body weight (kg)/height .Data regarding the sex of the infants, birth weight, birth height, and gestational age at delivery were obtained from the data recorded in the Maternal and Child Health Handbook by the obstetrician or midwife in charge of delivery. These data were based on birth registration. We used these data to diagnose the following outcomes: LBW, preterm birth, SGA, and AGA. LBW was defined as birth weight < 2,500 g, and preterm birth was defined as birth occurring at a gestational age < 37 weeks. SGA infants were diagnosed when the neonatal birth weight was below the 10th percentile of the standard birth weight curve for Japanese male and female infants.First, to confirm whether the results of this cohort were consistent with previous results, we used multiple logistic regression analysis to clarify the risk factors of LBW, SGA infants, and preterm birth in this cohort. The dependent variables were birth weight , intrauterine growth (SGA or not SGA), and gestational age at birth (preterm birth or no preterm birth). The independent variables were selected from previous reports regarding independent risk factors of LBW or SGA outcomes.Next, we carried out 4 analyses using multiple logistic regression models to clarify the relationship of maternal smoking during pregnancy with SGA infants and with preterm LBW infants. We defined the following 4 types of cases in this cohort: (1) LBW SGA infants, (2) LBW AGA infants, (3) LBW preterm infants, and (4) LBW full-term infants. The independent variables were the same as those used in the cohort study regarding LBW, SGA, and preterm infants.® software, version 9.1 .All analyses were conducted using SASIn this study, 1,329 pregnant women responded to the questionnaires administered at pregnancy registration. Of these, infant data were collected from 1,100 mothers (follow-up rate: 82.8%). Smoking during early pregnancy was reported by 72 (6.6%) mothers. Of the 81 (7.4%) LBW infants present, 47 (58.0%) were SGA, 34 (42.0%) were AGA, 25 (30.9%) were preterm, and 56 (69.1%) were full-term. The mean birth weight and gestational age (in weeks) of LBW, SGA, and preterm infants are listed in The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the maternal factors that influenced the LBW, SGA, and preterm birth outcomes are listed in Next, we carried out 2 multivariable analyses to compare the risk factors between LBW SGA infants and LBW AGA infants. Maternal smoking during early pregnancy was identified as a risk factor for LBW and SGA outcomes . On the other hand, no risk factor for the latter outcome in this analysis. In addition, we compared the risk factors between LBW preterm infants and LBW full-term infants. In the former, late registration of pregnancy was the only risk factor identified , and no other risk factors, including maternal smoking , were identified. In the latter, maternal smoking during early pregnancy was identified as a risk factor . 15 Maternal smoking during early pregnancy is a major risk factor for LBW; however, other risk factors for LBW remain unknown. Moreover, because LBW infants do not form a homogeneous group, we supposed that there are multiple etiologies responsible for LBW. In order to clarify these issues, we carried out an epidemiologic study by using a prospective cohort of pregnant women in a Japanese rural area.It is estimated that 40% of all cases of LBW occur due to hereditary factors, and the remaining 60% occur due to environmental factors.The follow-up rate in this study was 82.8%; the most common reasons for discontinuing follow up might be migration to another area or miscarriage. Moreover, the participants in our study included 3 infants with very LBW. Although we could not obtain information regarding the complication(s) in these 3 cases, the mothers of these infants did not smoke during early pregnancy. Thus, our results pertaining to the association between maternal smoking and outcome of pregnancy might be an underestimation.5,9,10,12,13 However, regarding the association between maternal smoking during pregnancy and preterm birth, contradictory results have been reported in previous studies. Some studies indicated the absence of such an association,16,17 whereas others indicated that maternal smoking during pregnancy was a risk factor for preterm birth.18,19 Even if an actual relationship exists between maternal smoking and preterm birth, our result might be attributed to the small sample size because the effect of smoking during pregnancy on preterm birth was suggested to be smaller than that on LBW and SGA.18 Moreover, maternal age at delivery and the sex of the infants were associated with preterm birth. These results were consistent with those of previous studies.19-22First, we carried out a cohort study to clarify the relationship between maternal smoking during early pregnancy and pregnancy outcomes, such as LBW, in this population. Our results suggested that maternal smoking during pregnancy was a risk factor for LBW and SGA outcomes. These results were similar to those of previous studies.23-29 However, no consistent conclusion was reached, especially, regarding an association between periodontal disease and LBW preterm infants.30 Further studies are required to reveal these risk factors.Next, we carried out 4 analyses to specify the risk factors for LBW SGA, LBW AGA, LBW preterm, and LBW full-term infants in this cohort. This cohort might be considered similar to the general population, based on the results of a previous cohort study regarding LBW, SGA infants, and preterm birth. Therefore, the bias influencing each group, such as socioeconomic background, might have been minimized in this study. In these analyses, we clarified that maternal smoking during early pregnancy was a major risk factor for LBW with SGA outcome but not for LBW with AGA outcome. These results in a prospective population-based study showed that there was a difference in the etiology of LBW infants. LBW AGA or LBW preterm outcomes were associated with other risk factors that were not considered in this study, such as periodontal disease or bacterial vaginosis.Moreover, the effect of maternal smoking during early pregnancy as a risk factor for LBW preterm infants was similar to its effect as a risk factor for LBW AGA infants, and its effects as a risk factor for LBW full-term and LBW SGA infants were similar. In this study, LBW preterm infants accounted for approximately 70% LBW AGA infants, while LBW full-term infants constituted approximately 80% LBW SGA infants. Our results reflect a strong association between intrauterine growth and gestational age at delivery in LBW infants.31 Late registration of pregnancy might be due to unawareness of or unwanted pregnancy. Therefore, our result was consistent with that of the previous report.Our results also indicated that late pregnancy registration (≥12 weeks) was a risk factor for LBW preterm infants. A previous study has reported that women with unwanted pregnancies had an increased likelihood of preterm delivery.Nevertheless, this study had some limitations. First, we recruited the participants over a 6-year period. During this time, some changes occurred in the participants’ background, such as increase in the knowledge of perinatal risk factors. These effects were beyond our control. Moreover, it is possible that women who delivered 2 or more children during this period might have participated 2 or more times in this study. However, we collected data from the pregnant women at the time pregnancy registration, and the BMI of mothers, which were the main genetic factors of physical development of the fetus, were controlled in statistical analysis. Therefore, we thought that the effect of this limitation of our study might be minimized.Second, we could not collect data regarding clinical complications such as periodontal disease or bacterial vaginosis because our study was based on a public health activity. Further studies to reveal these clinical risk factors and the interaction between these factors and previously well-known risk factors are required.Third, we could not obtain data regarding maternal smoking trends at various stages of pregnancy.Fourth, it is possible that the data regarding the analysis of preterm infants was insufficient because of the relatively small number of cases included. However, the OR of maternal smoking during pregnancy being associated with the preterm delivery was lesser than that of it being associated with LBW SGA infants. This result suggested the existence of different risk factors for LBW SGA infants and preterm birth.Despite these limitations, our study was based on community-based prospective data and had a high follow-up rate. Thus, our results were verified to have high internal validity. Moreover, the results of our cohort study were consistent with those of previous studies. This indicated that our questionnaire correctly reflected the lifestyles of the participants. Therefore, our results were verified to have high external validity as well.23-29 These results suggested that for the prevention of LBW, not only abstinence from smoking during pregnancy but also other methods such as establishing a clinical setting should be adopted.This prospective study indicated a difference in the risk factors for LBW SGA infants and LBW preterm infants. Moreover, LBW and preterm birth might be associated with other risk factors that were not considered in this study, such as periodontal disease or bacterial vaginosis.


AbstractHeloridae and Proctotrupidae (Proctotrupoidea) substantially updates the previous comprehensive checklist, dating from 1978. Country level data  is reported where known.A revised checklist of the British and Irish Heloridae and 39 Proctotrupidae (including only certainly recorded species) represents a 27% increase in the British list since 1978. Most species are still poorly known and there has been a dearth of taxonomic and faunistic work on the British and Irish fauna.A total of three  Hymenoptera fauna, that started with Hymenoptera checklist since 1978  are completely unknown biologically.This paper is part of a series of new checklists to the British and Irish nce 1978 . ProctotProctotrupoidea' has generally been a welcoming home to a variety of parasitoid groups and recognised as not being monophyletic  has recently gained acceptance  or identification in the British Isles uncertainmisident. has been misidentified as this namenomen dubium, a name of unknown or doubtful applicationnom. dub. nomen oblitum, ‘forgotten name’, does not have priority over a younger namenom. ob. nomen novum, a replacement namenom. nov. nomen nudum, an unavailable name, with no type specimennom. nud. preocc. name preoccupied (junior homonym)status revocatus, revived status stat. rev. unavailable not meeting the requirements of the International Code of Zoological Nomenclaturevar. variety, only available as a valid name under the provisions of article 45.6 of the ICZNAlternative versions of the checklist, as a formatted Word document and Excel spreadsheet, are provided here in the supplementary materials: Suppl. materials Photographs were taken using a Canon EOS 450D digital camera attached to a Leica MZ12 stereomicroscope and partially focused images were combined using Helicon Focus v.4.80 software.Förster, 1856Distribution data from Latreille, 1802COPELUS Provancher, 1881Sphexanomalipes Panzer, 1798ater Latreille, 1802paradoxusCopelus) Codrusparvulus Nees, 1834England, IrelandPanzer, 1801Panzer, 1805England, IrelandDisogmuspicicornis Förster, 1856subcompressusPhaenoserphus)   Proctotrupesaculeator Haliday, 1839aterCodrus) preocc.  Proctotrupesflavipes Provancher, 1881brevimanusSerphus)  Proctotrupeslongitarsis Thomson, 1858IrelandFörster, 1856Proctotrupesareolator Haliday, 1839aequator Förster, 1856discrepator Förster, 1856elegansProctotrupes)  Proctotrupesbasalis Thomson, 1858fuscitarsis Kieffer, 1907England, Scotland, IrelandKieffer, 1904Exallonyx:unplaced species of Exallonyxleviventris Kieffer, 1908 nom. dub., from England] Listed as British by perkinsi was then considered to be a junior synonym of foveolatus.[Proctotrupeslaricis Haliday, 1839nigricaudaSerphus)  Cryptoserphusperkinsi Nixon, 1942England, IrelandSupplementary material 1ProctotrupoideaChecklist of British and Irish Data type: formatted textBrief description: Word document version of the checklistFile: oo_74853.docxBroad, G.R.Supplementary material 2ProctotrupoideaChecklist of British and Irish Data type: spreadsheetBrief description: Excel spreadsheet version of the checklistFile: oo_84638.xlsxBroad, G.R.