Influence of Gestational Age and Parental Education on Executive Functions of Children Born Very Preterm

Background: Children born very preterm (<32 weeks’ gestational age; VPT) and/or very low birth weight (<1500 g; VLBW) are at high risk of deficits in executive functions, namely inhibition, working memory, and shifting. Both, gestational age and socioeconomic factors, such as parental education, are known to influence executive functions, with children born at lower gestational age and with lower educated parents displaying worse executive skills. This study aimed to investigate if maternal and paternal education moderated the relationship between gestational age and executive functions in VPT/VLBW children aged 8-12 years. It was hypothesised that the disadvantageous effect of low gestational age could be buffered more easily in families with higher educational background. Methods: Sixty VPT/VLBW children born in the cohort of 1998-2003 were recruited. All children completed executive function tasks (inhibition, working memory, and shifting). Results: There was a significant dose-response-relationship between gestational age and inhibition, with children being born at earlier gestational age showing worse inhibition. However, neither maternal nor paternal education moderated the relationship between gestational age and executive functions significantly. Conclusion: children than parental education. The disadvantageous effect of low gestational age was equal in children with higher and lower educated parents. However, the impact of gestational age and parental education on executive functions may differ depending on the socioeconomic spectrum of the study sample.

Epidemiologic survey in Swiss group-housed breeding rabbits: extent of lesions and potential risk factors

In Switzerland, group-housing for breeding rabbit does is not explicitly required by law, but label programmes, as well as the general public and animal welfare groups, are advocating it. Although group-housing is of great benefit to the gregariously living rabbits, the establishment of a social hierarchy within the group might lead to stress and lesions. In the present epidemiological study, lesions were scored twice on 30% of the breeding does on all 28 commercial Swiss farms with group-housed breeding does. Additionally, a detailed questionnaire was filled out with all producers to determine risk factors potentially associated with lesions. Data were analysed using hierarchical proportional odds models. About 33% of the does examined had lesions, including wounds that were almost healed and small scratches. Severe lesions were counted on 9% of the animals. Differences between seasons in lesions score were identified, with the extent of lesions being higher in summer than in spring. Fewer lesions occurred on farms on which mastitis was more common. More lesions were found on farms where the does were isolated between littering and artificial insemination than on farms without isolation. According to the producers, most of the aggression occurred directly after the isolation phase when the does were regrouped again. We conclude that lesions in group-housed breeding does might be reduced by appropriate reproductive management.

Xenobiotic Metabolism Genes and Clubfoot

Idiopathic or isolated clubfoot is a common orthopedic birth defect that affects approximately 135,000 children worldwide. It is characterized by equinus, varus and adductus deformities of the ankle and foot. Correction of clubfoot involves months of serial manipulations, castings and bracing, with surgical correction needed in forty percent of cases. Multifactorial etiology has been suggested in numerous studies with both environmental and genetic factors playing an etiologic role. Maternal smoking during pregnancy is the only common environmental factor that has consistently been shown to increase the risk for clubfoot. Moreover, a positive family history of clubfoot and maternal smoking increases the risk of clubfoot twenty fold. These findings suggest that genetic variation in smoking metabolism genes may increase susceptibility to clubfoot. Based on this reasoning, we interrogated eight candidate genes, chosen based on their involvement in phase 1 and 2 cigarette smoke metabolism. Twenty-two SNPs and two null alleles in eight genes (CYP1A1, CYP1A2, CYP1B1, CYP2A6, EPHX1, NAT2, GSTM1 and GSTT1) were genotyped in a dataset composed of nonHispanic white and Hispanic multiplex and simplex families. Only one SNP in CYP1A1, rs1048943, had significantly altered transmission in the aggregate and multiplex NHW datasets (p=0.003 and p=0.009). Perturbation of CYP1A1 by rs1048943 polymorphism causes an increase in the amount of harmful, adduct forming metabolic intermediates. A significant gene interaction between EPHX1 and NAT2 was also found (p=0.007). This interaction may affect the metabolism of harmful metabolic intermediates. Additionally, marginal interactions were found for other xenobiotic genes and these interactions may play a contributory role in clubfoot. Importantly, for CYP1A2, significant maternal (p=0.03; RR=1.24; 95% CI: 1.04-1.44) and fetal (p=0.01; RR=1.33; 95% CI: 1.13-1.54) genotypic effects were identified suggesting that both maternal and fetal genotypes impact normal limb development. No association was found for maternal smoking status and tobacco metabolism genes. Together, these results suggest that xenobiotic metabolism genes may play a contributory role in the etiology of clubfoot regardless of maternal smoking status and may impact foot development through perturbation of tobacco metabolic pathways.

Humane Orientation as a New Cultural Dimension of the GLOBE Project: A Validation Study of the GLOBE Scale and Out-Group Humane Orientation in 25 Countries

We validate, extend, and empirically and theoretically criticize the cultural dimension of humane orientation of the project GLOBE (Global Leadership and Organizational Behavior Effectiveness Research Program). Theoretically, humane orientation is not just a one-dimensionally positive concept about being caring, altruistic, and kind to others as discussed by Kabasakal and Bodur (2004), but there is also a certain ambivalence to this concept. We suggest differentiating humane orientation toward in-group members from humane orientation toward out-group members. A multicountry construct validation study used student samples from 25 countries that were either high or low in humane orientation (N = 876) and studied their relation to the traditional GLOBE scale and other cultural-level measures (agreeableness, religiosity, authoritarianism, and welfare state score). Findings revealed a strong correlation between humane orientation and agreeableness, welfare state score, and religiosity. Out-group humane orientation proved to be the more relevant subfacet of the original humane orientation construct, suggesting that future research on humane orientation should make use of this measure instead of the vague original scale. The ambivalent character of out-group humane orientation is displayed in its positive correlation to high authoritarianism. Patriotism was used as a control variable for noncritical acceptance of one’s society but did not change the correlations. Our findings are discussed as an example of how rigid expectations and a lack of tolerance for diversity may help explain the ambivalent nature of humane orientation

Ultrasound feedback and motivational interviewing targeting smoking cessation in the second and third trimesters of pregnancy.

INTRODUCTION: Cigarette smoking during pregnancy is associated with poor maternal and child health outcomes. Effective interventions to increase smoking cessation rates are needed particularly for pregnant women unable to quit in their first trimester. Real-time ultrasound feedback focused on potential effects of smoking on the fetus may be an effective treatment adjunct, improving smoking outcomes. METHODS: A prospective randomized trial was conducted to evaluate the efficacy of a smoking cessation intervention consisting of personalized feedback during ultrasound plus motivational interviewing-based counseling sessions. Pregnant smokers (N = 360) between 16 and 26 weeks of gestation were randomly assigned to one of three groups: Best Practice (BP) only, Best Practice plus ultrasound feedback (BP+US), or Motivational Interviewing-based counseling plus ultrasound feedback (MI+US). Assessments were conducted at baseline and end of pregnancy (EOP). RESULTS: Analyses of cotinine-verified self-reported smoking status at EOP indicated that 10.8% of the BP group was not smoking at EOP; 14.2% in the BP+US condition and 18.3% who received MI+US were abstinent, but differences were not statistically significant. Intervention effects were found conditional upon level of baseline smoking, however. Nearly 34% of light smokers (< or =10 cigarettes/day) in the MI+US condition were abstinent at EOP, followed by 25.8% and 15.6% in the BP+US and BP conditions, respectively. Heavy smokers (>10 cigarettes/day) were notably unaffected by the intervention. DISCUSSION: Future research should confirm benefit of motivational interviewing plus ultrasound feedback for pregnant light smokers and explore mechanisms of action. Innovative interventions for pregnant women smoking at high levels are sorely needed.

Tilapia sex determination: Where temperature and genetics meet

This review deals with the complex sex determining system of Nile tilapia, Oreochromis niloticus, governed by the interactions between a genetic determination and the influence of temperature, shown in both domestic and wild populations. Naturally sex reversed individuals are strongly suggested in two wild populations. This can be due to the masculinising temperatures which some fry encounter during their sex differentiation period when they colonise shallow waters, and/or to the influence of minor genetic factors. Differences regarding a) thermal responsiveness of sex ratios between and within Nile tilapia populations, b) maternal and paternal effects on temperature dependent sex ratios and c) nearly identical results in offspring of repeated matings, demonstrate that thermosensitivity is under genetic control. Selection experiments to increase the thermosensitivity revealed high responses in the high and low sensitive lines. The high-line showed ~ 90% males after 2 generations of selection whereas the weakly sensitive line had 54% males. This is the first evidence that a surplus of males in temperature treated groups can be selected as a quantitative trait. Expression profiles of several genes (Cyp19a, Foxl2, Amh, Sox9a,b) from the gonad and brain were analysed to define temperature action on the sex determining/differentiating cascade in tilapia. The coexistence of GSD and TSD is discussed.

Human placental lactogen enhancer: Tissue specificity and binding with specific proteins

Human placental lactogen (hPL) is a 22,000 dalton protein hormone produced in the placenta. The physiological actions of hPL are not well understood but its major activity is to regulate both maternal and fetal metabolism. hPL stimulates maternal lipolysis increasing free fatty acids in the maternal blood, allowing their use as an energy source by the mother, and sparing glucose for the fetus. It may also act as a growth promoting hormone for the fetus. hPL is produced in increasing amounts as pregnancy progresses. At term, hPL accounts for 10% of protein and 5% of total RNA in the placenta. This high level of hPL production is tissue-specific, as hPL is only produced in the placenta by syncytiotrophoblast cells.^ The objective of this work was to understand the mechanism by which such high levels of hPL are produced in a tissue-specific manner. A transcriptional enhancer found 2.2 kb 3$\sp\prime$ to one of the hPL genes (hPL$\sb3$) may explain the regulation of hPL expression. Transient transfection experiments using the hPL-producing human choriocarcinoma cell line JEG-3 localized the hPL enhancer to a 138 bp core element. This 138 bp sequence was found to be tissue specific in its actions as it did not promote transcription in heterologous cell lines. Gel mobility shift assays showed the hPL enhancer interacts specifically with nuclear proteins unique to hPL-producing cells. Within the 138 bp enhancer a 22 bp region was shown to be protected from DNase I digestion due to binding of proteins derived from placental nuclear extracts. Proteins binding this region of the enhancer may be instrumental in the tissue specific activity of the hPL enhancer. ^

The influence of staff and organizational characteristics on social environment in substance abuse treatment facilities

The staff of 20 substance abuse treatment facilities were administered the Ward Atmosphere Scale, an instrument which measures treatment environment. Ten facilities were freestanding and ten were hospital based, and were drawn from a large, not-for-profit national chain using a random selection process. Controlling for several staff and facility attributes, it was found that no substantial effects on treatment environment existed due to facility type, freestanding or hospital-based. Implications of the study exist in selection of facility type for purchasers of substance abuse treatment and for the hiring and training of clinical staff for treatment facilities. Study findings also suggest that inadequate or insufficient measures exist to examine the construct 'treatment environment'. ^

The determinants of physician and pharmacist utilization and equity of access under Korean universal health insurance

This study examines the social and behavioral determinants of two types of primary care, seeing a physician or a pharmacist, for Koreans and evaluates the equity of the Korean national health insurance system. The study applies the Aday and Andersen access framework to cross-sectional data from the 1992 Korean National Health Interview Survey (N = 21,841).^ The study found that in Korea, the elderly were most likely, and children least likely, to have used physician services. Women, household heads, those in small families, and the less educated were more likely than their counterparts to use physician and pharmacist services. Health status and need were important determinants of Koreans seeing a doctor or a pharmacist. Differences in need substantially accounted for the original differences observed between subgroups. Resources associated with having insurance coverage, a regular source of care, and place of residence (rural/urban) ameliorated to some extent the subgroup differences in the use of physicians' and pharmacists' services among Koreans. They were also major independent predictors of access. Having insurance remains a particularly important predictor of who uses physician services. Among the insured, trade-offs in the use of physician and pharmacist services were found in the current system, i.e., uninsured and poor Koreans were more likely to use pharmacist services, while insured and rural Koreans were more likely to use doctor services. Among the insured, cost sharing rates are lower for physician than for pharmacist services. Self-employed persons were less likely than government and industrial workers to use physician services. An underlying expectation under universal health insurance was that the Korean health care system would be equitable. The research results, however, did not fully support this expectation.^ The policy implications of these findings are that measures are required to extend insurance coverage to the uninsured, to equalize differences in benefit packages between health plans, and to expand the availability of physicians in rural areas. Further research is also needed to understand those who do not currently have a regular source of care and why and the access barriers that may exist for selected demographic subgroups (those in large families and unmarried or divorced/widowed persons). ^

Factors influencing the attitudes of cattle veterinarians, farmers, and claw trimmers towards the pain associated with the treatment of sole ulcers and the sensitivity to pain of dairy cows

This study assessed the attitudes of personnel involved in therapeutic claw trimming of dairy cattle in Switzerland towards pain associated with sole ulcers and their treatment. Data from 77 farmers, 32 claw trimmers, and 137 cattle veterinarians were used. A large range of factors were associated with whether the respondents thought that anaesthesia during the treatment of sole ulcers was beneficial; these included year of graduation, work experience, attitude to costs of analgesia, perception of competition between veterinarians and claw trimmers, estimation of pain level associated with treatment, estimated sensitivity of dairy cows to pain, knowledge of the obligation to provide analgesia, and whether the respondent thought lesion size and occurrence of defensive behaviour by the cow were important. Respondents' estimation of the pain level associated with sole ulcer treatment was linked to frequency of therapeutic claw trimming, age, farmers' income, estimated knowledge of the benefits of analgesia, and estimated sensitivity of dairy cows to pain. The latter factor was associated with profession, frequency of therapeutic claw trimming, capability of pain recognition, opinion on the benefits of analgesia, knowledge of the obligation to provide analgesia, and self-estimation of the ability to recognise pain. Improving the knowledge of personnel involved in therapeutic claw trimming with regard to pain in dairy cows and how to alleviate it is crucial if management of pain associated with treatment of sole ulcer and the welfare of lame cows are to be optimised.

Seals and the Need for more Deference to Vienna by WTO Adjudicators

This paper asks how World Trade Organization (WTO) panels and the Appellate Body (AB) take public international law (PIL) into account when interpreting WTO rules as a part of international economic law (IEL). Splendid isolation of the latter is not new; indeed it is intended by the negotiators of the Understanding on the Settlement of Disputes (DSU). At the same time, the Vienna Convention on the Law of Treaties (VCLT) is quite clear when it provides the general rules and the supplementary means of treaty interpretation. Despite such mandatory guidance, WTO adjudicators (when given a choice and assuming they see the conflict) prefer deference to WTO law over deference to Vienna and take a dogmatic way out of interpretation quandaries. The AB and panels make abundant reference to Vienna, though less so to substantive PIL. Often times, however, they do so simply in order to buttress their findings of violations of WTO rules. Perhaps tellingly, however, none of the reports in EC – Seals contains even a single mention of VCLT, despite numerous references to international standards addressing indigenous rights and animal welfare. In the longer term, and absent a breakthrough on the negotiation front, this pattern of carefully eschewing international treaty law and using PIL just for the sake of convenience could have serious consequences for the credibility and acceptance of the multilateral trading system. Following the adage ‘negotiate or litigate’ recourse to WTO dispute settlement increases when governments are less ready to make treaty commitments commensurate with the challenges of globalisation. This is true even for ‘societal choice’ cases on the margins of classic trade disputes. We will argue here that it is precisely for cases such as these that VCLT and PIL should be used more systematically by panels and the AB. Failing that, instead of building bridges for more coherent international regulation, WTO adjudicators could burn those same bridges which the DSU interpretation margin leaves open for accomplishing their job which is to find a ‘positive solution’. Worse, judicial incoherence could return to WTO dispute settlement like a boomerang and damage the credibility and thus the level of acceptance of the multilateral trading system per se.

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.

Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol.

OBJECTIVE To provide information on pregnancy outcomes in women receiving certolizumab pegol (CZP). METHODS The UCB Pharma safety database was searched for pregnancies through to September 1, 2014. Reports for maternal and paternal CZP exposure were included and outcomes examined, and data on CZP exposure, pregnancy, comorbidities, and infant events were extracted by 2 independent reviewers. Concomitant medications and disease activity were reviewed for clinical trial patients. RESULTS Of 625 reported pregnancies, 372 (59.5%) had known outcomes. Paternal exposure pregnancies (n = 33) reported 27 live births, 4 miscarriages, 1 induced abortion, and 1 stillbirth. Maternal exposure pregnancies (n = 339) reported 254 live births, 52 miscarriages, 32 induced abortions, and 1 stillbirth. Almost all reported pregnancies had exposure to CZP in the first trimester, when organogenesis takes place, and a third of them continued the drug into the second and/or third trimesters. The most frequent indications for maternal CZP use were Crohn disease (192/339) and rheumatic diseases (118/339). Twelve cases of congenital malformation and a single neonatal death were reported. CONCLUSION Analysis of pregnancy outcomes after exposure to CZP supports previous reports, suggesting a lack of harmful effect of maternal CZP exposure on pregnancy outcomes. However, additional data from a larger number of outcomes after exposure and studies including an unexposed comparison group are required to fully evaluate CZP safety and tolerability in pregnancy.

The role of drug use in welfare to work: Evidence from Houston, Texas

The purpose of this study is to examine the prevalence of drug abuse among welfare recipients in Houston, TX and compare the work activities and employment barriers of drug abusers in order to better understand the potential effects of welfare reform for this population. Four hypotheses were tested comparing the work activities and employment barriers of drug abusers to others on welfare and the relative importance of drug abuse and employment barriers in predicting work activity. ^ This cross-sectional study examined the characteristics and work activities of 447 welfare recipients (81 drug abusers and 366 non-abusers) who were surveyed between October 1998 and April 1999 in Houston, TX. Subjects were introduced and recruited to participate in the study through a flyer, door to door visits, and peer driven recruitment/referral. ^ About 18% were found to be drug abusers, which is consistent with the national average (10–33%) among welfare recipients. Compared to others on welfare, drug abusers were less involved in work activities, and had more employment barriers. Employment barriers were found to be more predictive of welfare to work activities than drug abuse. The results suggest that alleviating employment barriers should be stressed in programs aimed at welfare recipients with drug abuse problems. ^