Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia

Chromosome 5q22-33 is a region where studies have repeatedly found evidence for linkage to schizophrenia. In this report, we took a stepwise approach to systematically map this region in the Irish Study of High Density Schizophrenia Families (ISHDSF, 267 families, 1337 subjects) sample. We typed 289 SNPs in the critical interval of 8 million basepairs and found a 758 kb interval coding for the SPEC2/PDZ-GEF2/ACSL6 genes to be associated with the disease. Using sex and genotype-conditioned transmission disequilibrium test analyses, we found that 19 of the 24 typed markers were associated with the disease and the associations were sex-specific. We replicated these findings with an Irish case-control sample (657 cases and 414 controls), an Irish parent-proband trio sample (187 families, 564 subjects), a German nuclear family sample (211 families, 751 subjects) and a Pittsburgh nuclear family sample (247 families, 729 subjects). In all four samples, we replicated the sex-specific associations at the levels of both individual markers and haplotypes using sex- and genotype-conditioned analyses. Three risk haplotypes were identified in the five samples, and each haplotype was found in at least two samples. Consistent with the discovery of multiple estrogen-response elements in this region, our data showed that the impact of these haplotypes on risk for schizophrenia differed in males and females. From these data, we concluded that haplotypes underlying the SPEC2/PDZ-GEF2/ACSL6 region are associated with schizophrenia. However, due to the extended high LD in this region, we were unable to distinguish whether the association signals came from one or more of these genes.

First steps: study protocol for a randomized controlled trial of the effectiveness of the Group Family Nurse Partnership (gFNP) program compared to routine care in improving outcomes for high-risk mothers and their children and preventing abuse

Background: Evidence from the USA suggests that the home-based Family Nurse Partnership program (FNP), extending from early pregnancy until infants are 24 months, can reduce the risk of child abuse and neglect throughout childhood. FNP is now widely available in the UK. A new variant, Group Family Nurse Partnership (gFNP) offers similar content but in a group context and for a shorter time, until infants are 12 months old. Each group comprises 8 to 12 women with similar expected delivery dates and their partners. Its implementation has been established but there is no evidence of its effectiveness.

Methods/Design: The study comprises a multi-site randomized controlled trial designed to identify the benefits of gFNP compared to standard care. Participants (not eligible for FNP) must be either aged <20 years at their last menstrual period (LMP) with one or more previous live births, or aged 20 to 24 at LMP with low educational qualifications and no previous live births. 'Low educational qualifications' is defined as not having both Maths and English Language GCSE at grade C or higher or, if they have both, no more than four in total at grade C or higher. Exclusions are: under 20 years and previously received home-based FNP and, in either age group, severe psychotic mental illness or not able to communicate in English. Consenting women are randomly allocated (minimized by site and maternal age group) when between 10 and 16 weeks pregnant to either to the 44 session gFNP program or to standard care after the collection of baseline information. Researchers are blind to group assignment. The primary outcomes at 12 months are child abuse potential based on the revised Adult-Adolescent Parenting Inventory and parent/infant interaction coded using the CARE Index based on a video-taped interaction. Secondary outcomes are maternal depression, parenting stress, health related quality of life, social support, and use of services.

Discussion: This is the first study of the effectiveness of gFNP in the UK. Results should inform decision-making about its delivery alongside universal services, potentially enabling a wider range of families to benefit from the FNP curriculum and approach to supporting parenting.

Parents' experiences of applied behaviour analysis (ABA)-based interventions for children diagnosed with autistic spectrum disorder

Applied behaviour analysis (ABA)-based programmes are endorsed as the gold standard for treatment of children with autistic spectrum disorder (ASD) in most of North America. This is not the case in most of Europe, where instead a non-specified 'eclectic' approach is adopted. We explored the social validity of ABA-based interventions with 15 European families who had experience with home-based, mainly self-managed, ABA-based programmes for their own child/ren with ASD. The results of the study highlighted the overwhelmingly positive impact that ABA-based interventions had on their children in areas such as social skills, challenging behaviour, communication, gross and fine motor skills, concentration, interaction, independence, overall quality of life and, most importantly, a feeling of hope for the future. Implications for European policy on ASD are discussed. © 2013 NASEN.

Thermotropic phase boundaries in classic ferroelectrics

High-performance piezoelectrics are lead-based solid solutions that exhibit a so-called morphotropic phase boundary, which separates two competing phases as a function of chemical composition; as a consequence, an intermediate low-symmetry phase with a strong piezoelectric effect arises. In search for environmentally sustainable lead-free alternatives that exhibit analogous characteristics, we use a network of competing domains to create similar conditions across thermal inter-ferroelectric transitions in simple, lead-free ferroelectrics such as BaTiO 3 and KNbO 3. Here we report the experimental observation of thermotropic phase boundaries in these classic ferroelectrics, through direct imaging of low-symmetry intermediate phases that exhibit large enhancements in the existing nonlinear optical and piezoelectric property coefficients. Furthermore, the symmetry lowering in these phases allows for new property coefficients that exceed all the existing coefficients in both parent phases. Discovering the thermotropic nature of thermal phase transitions in simple ferroelectrics thus presents unique opportunities for the design of 'green' high-performance materials.

Neonatal intensive care and late preterm infants:Health and family functioning at three years

Background: Late preterm infants (LPIs), born at 34 + 0 to 36 + 6 weeks of gestation contribute a significant proportion of all neonatal intensive care (NIC) admissions and are regarded as being at risk of adverse outcomes compared to term-born infants.

Aim: To explore the health outcomes and family functioning of LPIs who required neonatal intensive care, at three years of age.

Study design and subjects: This cohort study included 225 children born late preterm, between 1 January and 31 December 2006 in Northern Ireland. Children admitted for NIC (study group, n = 103) were compared with children who did not require NIC or who required special care only for up to three days (comparison group, n = 122).

Outcome measures
Health outcomes were measured using the Health Status Questionnaire, health service usage by parent report and family functioning using the PedsQL™ Family Impact Module.

Results: LPIs who required NIC revealed similar health outcomes at three years in comparison to those who did not. Despite this, more parents of LPIs who required NIC reported visiting their GP and medical specialists during their child's third year of life. Differences in family functioning were also observed with mothers of LPIs who required NIC reporting, significantly lower levels of social and physical functioning, increased difficulties with communication and increased levels of worry.

Conclusions: LPIs were observed to have similar health outcomes at three years of age regardless of NIC requirement. The increase in GP and medical specialist visits and family functioning difficulties observed among those infants who required NIC merits further investigation.

Abbreviations: LPI, late preterm infant; NIC, neonatal intensive care; HSQ, Health Status Questionnaire; GP, general practitioner

'Big, strong and healthy'. Young children's identification of food and drink that contribute to healthy growth

Growing awareness of the importance of healthy diet in early childhood makes it important to chart the development of children's understanding of food and drink. This study aimed to document young children's evaluation of food and drink as healthy, and to explore relationships with socioeconomic status, family eating habits, and children's television viewing. Data were gathered from children aged 3-5. years (. n=. 172) in diverse socioeconomic settings in Ireland, and from their parents. Results demonstrated that children had very high levels of ability to identify healthy foods as important for growth and health, but considerably less ability to reject unhealthy items, although knowledge of these increased significantly between ages 3 and 5. Awareness of which foods were healthy, and which foods were not, was not related to family socioeconomic status, parent or child home eating habits, or children's television viewing. Results highlighted the importance of examining young children's response patterns, as many of the youngest showed a consistent 'yes bias'; however, after excluding these responses, the significant findings remained. Findings suggest it is important to teach children about less healthy foods in the preschool years. © 2013 Elsevier Ltd.

Antioxidant Activity of Sesame (Seasamum indicum L.) Cake Extract for the Stabilization of Olein Based Butter

This study investigated the effect of ethanolic sesame cake extract on oxidative stabilization of olein based butter. Fractionation of cream was performed by the dry fractionation technique at 10 °C, ethanolic sesame cake extract (SCE) was incorporated into olein butter at three different concentrations; 50, 100, 150 ppm (T1, T2, T3) and compared with a control. The total phenolic content of SCE was 1.72 (mg gallic acid equivalent g−1 dry weight). The HPLC characterization of ethanolic sesame cake revealed the presence of antioxidant substances viz. sesamol, sesamin and sesamolin in higher extents. The DPPH free radical scavenging activity of SCE was 83 % as compared to 64 and 75 % in BHA and BHT. Fractionation of milk fat at 10 °C significantly (p < 0.05) influenced the fatty acid profile of olein and stearin fractions from the parent milk fat. Concentration of oleic acid and linoleic acid in olein fraction was 29.62 and 33.46 % greater than the parent milk fat. The loss of C18:1 in 90 days stored control and T3 was 24.37 and 3.58 %, respectively, 58 % C18:2 was broken down into oxidation products over 8.55 % loss in T3. The peroxide value of control, T1, T2, BHT and T3 in the Schaal oven test was 8.59, 8.12, 5.34, 4.52 and 2.49 (mequiv O2/kg). The peroxide value and anisidine value of 3 months stored control and T3 were 1.21, 0.42 (mequiv O2/kg) and 27.25, 13.25, respectively. The concentration of conjugated dienes in T3 was substantially less than the control. The induction period of T3 was considerably higher than BHT with no difference in sensory characteristics (p > 0.05). Ethanolic SCE can be used for the long-term preservation of olein butter, with acceptable sensory characteristics.

Adolescent ecstasy use and depression: cause and effect, or two outcomes of home environment?

Background: This study assessed the association between adolescent ecstasy use and depressive symptoms in adolescence. Methods: The Belfast Youth Development Study surveyed a cohort annually from age 11 to 16 years. Gender, Strengths and Difficulties Questionnaire emotional subscale, living arrangements, parental affluence, parent and peer attachment, tobacco, alcohol, cannabis and ecstasy use were investigated as predictors of Short Mood and Feelings Questionnaire (SMFQ) outcome. Results: Of 5371 respondents, 301 (5.6%) had an SMFQ > 15, and 1620 (30.2) had missing data for SMFQ. Around 8% of the cohort had used ecstasy by the end of follow-up. Of the non-drug users, ∼2% showed symptoms of depression, compared with 6% of those who had used alcohol, 6% of cannabis users, 6% of ecstasy users and 7% of frequent ecstasy users. Without adjustment, ecstasy users showed around a 4-fold increased odds of depressive symptoms compared with non-drug users [odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.10, 0.68]. Further adjustment for living arrangements, peer and parental attachment attenuated the association to under a 3-fold increase (OR = 0.37; 95% CI = 0.15, 0.94). There were no differences by frequency of use. Conclusions: Ecstasy use during adolescence may be associated with poorer mental health; however, this association can be explained by the confounding social influence of family dynamics. These findings could be used to aid effective evidence-based drug policies, which concentrate criminal justice and public health resources on reducing harm.

The influence of parents, older siblings, and non-parental care on infant development at nine months of age

Background: The majority of research examining the influence of social environment on early child development suggests benefits to two-parent households, but contradictory evidence for the effects of siblings. The aims of the present study were to examine the influence of the child's proximal social environment, and the effects of interactions between socioeconomic status and social environment on developmental outcomes.

Methods: Primary caregivers of a representative sample of 10,748 nine-month-old infants in Ireland completed the Ages and Stages Questionnaire and provided information on social environment. Adjustment was made for infant and maternal characteristics, household income, and area where the child was living at the time of the study. Further analyses tested for interactions between social environment and household income.

Results: Binary logistic regressions indicated no effects for number of parents in the household. However, the presence of siblings in the household was a consistent predictor of failing to reach milestones in communication, gross motor, problem-solving, and personal-social development. Furthermore, there was a gradient of increasing likelihood of failing in gross motor, problem-solving, and personal-social development with increasing numbers of siblings. Care by a grandparent decreased the likelihood of failing in communication and personal-social development.

Conclusions:These findings do not support the majority of research that finds positive benefits for two-parent households. Similarly, the findings suggest limited effects for non-parental care. However, the observed negative effects of siblings support both the confluence and resource dilution models of sibling effect. Examination of follow-up data may elucidate current findings.

Tidally Distorted Exoplanets: Density Corrections for Short-period Hot-Jupiters Based Solely on Observable Parameters

The close proximity of short-period hot-Jupiters to their parent star means they are subject to extreme tidal forces. This has a profound effect on their structure and, as a result, density measurements that assume that the planet is spherical can be incorrect. We have simulated the tidally distorted surface for 34 known short-period hot-Jupiters, assuming surfaces of constant gravitational equipotential for the planet, and the resulting densities have been calculated based only on observed parameters of the exoplanet systems. Comparing these results to the density values, assuming the planets are spherical, shows that there is an appreciable change in the measured density for planets with very short periods (typically less than two days). For one of the shortest-period systems, WASP-19b, we determine a decrease in bulk density of 12% from the spherical case and, for the majority of systems in this study, this value is in the range of 1%-5%. On the other hand, we also find cases where the distortion is negligible (relative to the measurement errors on the planetary parameters) even in the cases of some very short period systems, depending on the mass ratio and planetary radius. For high-density gas planets requiring apparently anomalously large core masses, density corrections due to tidal deformation could become important for the shortest-period systems.

Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis

Background Metronidazole is the most commonly used antimicrobial for Bacteroides fragilis infections and is recommended for prophylaxis of colorectal surgery. Metronidazole resistance is increasing and the mechanisms of resistance are not clear.

Methods A transposon mutant library was generated in B. fragilis 638R (BF638R) to identify the genetic loci associated with resistance to metronidazole.

Results Thirty-two independently isolated metronidazole-resistant mutants had a transposon insertion in BF638R_1421 that encodes the ferrous transport fusion protein (feoAB). Deletion of feoAB resulted in a 10-fold increased MIC of metronidazole for the strain. The metronidazole MIC for the feoAB mutant was similar to that for the parent strain when grown on media supplemented with excess iron, suggesting that the increase seen in the MIC of metronidazole was due to reduced cellular iron transport in the feoAB mutant. The furA gene repressed feoAB transcription in an iron-dependent manner and disruption of furA resulted in constitutive transcription of feoAB, regardless of whether or not iron was present. However, disruption of feoAB also diminished the capacity of BF638R to grow in a mouse intraperitoneal abscess model, suggesting that inorganic ferrous iron assimilation is essential for B. fragilis survival in vivo.

Conclusions Selection for feoAB mutations as a result of metronidazole treatment will disable the pathogenic potential of B. fragilis and could contribute to the clinical efficacy of metronidazole. While mutations in feoAB are probably not a direct cause of clinical resistance, this study provides a key insight into intracellular metronidazole activity and the link with intracellular iron homeostasis.

Characterization of the Kepler-101 planetary system with HARPS-N. A hot super-Neptune with an Earth-sized low-mass companion

We characterize the planetary system Kepler-101 by performing a combined differential evolution Markov chain Monte Carlo analysisof Kepler data and forty radial velocities obtained with the HARPS-N spectrograph. This system was previously validated and iscomposed of a hot super-Neptune, Kepler-101b, and an Earth-sized planet, Kepler-101c. These two planets orbit the slightly evolvedand metal-rich G-type star in 3.49 and 6.03 days, respectively. With mass Mp = 51.1+5.1−4.7 M⊕, radius Rp = 5.77+0.85−0.79 R⊕, and density ρp = 1.45+0.83 −0.48 g cm−3, Kepler-101b is the first fully characterized super-Neptune, and its density suggests that heavy elements makeup a significant fraction of its interior; more than 60% of its total mass. Kepler-101c has a radius of 1.25+0.19−0.17 R⊕, which implies theabsence of any H/He envelope, but its mass could not be determined because of the relative faintness of the parent star for highly precise radial-velocity measurements (Kp = 13.8) and the limited number of radial velocities. The 1σ upper limit, Mp < 3.8 M⊕, excludes a pure iron composition with a probability of 68.3%. The architecture of the planetary system Kepler-101 − containing aclose-in giant planet and an outer Earth-sized planet with a period ratio slightly larger than the 3:2 resonance − is certainly of interest for scenarios of planet formation and evolution. This system does not follow the previously reported trend that the larger planet has the longer period in the majority of Kepler systems of planet pairs with at least one Neptune-sized or larger planet.

Determination of the persistence of dimetridazole, metronidazole and ronidazole residues in black tiger shrimp (Penaeus monodon) tissue and stability during cooking

The depletion of three banned nitroimidazole drugs (dimetridazole (DMZ), metronidazole (MNZ) and ronidazole (RNZ)) was investigated in black tiger shrimp (Penaeus monodon) following in-water medication. The highest concentrations of residues were measured immediately after the 24 h immersion (day 0). At this time, MNZ and MNZ-OH residues were measured in shrimp tissue samples at concentrations ranging from 361–4189 and 0.28–6.6 μg kg−1, respectively. DMZ and its metabolites HMMNI ranged in concentration between 31509–37780 and 15.0–31.9 μg kg−1, respectively. RNZ and HMMNI concentrations ranged 14530–24206 and 25.0–55 μg kg−1, respectively. MNZ, DMZ and RNZ were the more persistent marker residues and can be detected for at least eight days post-treatment. MNZ-OH was only detectable on day 0 following treatment with MNZ. HMMNI residues were only detectable up to day 1 (0.97–3.2 μg kg−1) or 2 (1.2–4.5 μg kg−1) following DMZ and RNZ treatment, respectively. The parent drugs, MNZ, DMZ and RNZ were still measureable on day 8 at 0.12–1.00, 40.5–55 and 8.8–18.7 μg kg−1, respectively. The study also investigated the stability of nitroimidazole residues under various cooking procedures (frying, grilling, boiling and boiling followed by microwaving). The experiments were carried out in shrimp muscle tissue containing both high and low concentrations of these residues. Different cooking procedures showed the impact on nitroimidazole residue concentration in shrimp tissuetheir concentration depleted significantly, but partially, by boiling and/or microwaving but the compounds were largely resistant to conventional grilling or frying. Cooking cannot therefore be considered as a safeguard against harmful nitroimidazole residues in shrimp.