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In 785 mother–child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7–15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7–15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health.
Rapid weight gain in infancy and low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) at birth are associated with increased adiposity later in life. The association between placental LCPUFA delivery and weight gain in infancy is poorly understood. We sought to determine the relationships between maternal phenotype, placental fatty acid transporter expression and offspring growth patterns over the first 6 months. Placental tissue and cord blood were collected at term delivery from women with uncomplicated pregnancies. Offspring body composition measurements were recorded 1 day and 6 months after birth. Body mass index (BMI) z-scores were determined using World Health Organization 2006 reference data. Body phenotype patterns were compared among offspring who had an increase in BMI z-score and those who had a decrease. High skinfold thickness at birth and positive change in BMI z-scores during infancy were associated with low neonatal n-3 LCPUFA plasma levels (r=−0.46, P=0.046) and high saturated fatty acids levels (r=0.49, P=0.034). Growth of skinfolds over 6 months of age was associated with placental fatty acid transporter gene expression. Change in BMI z-score in the first 6 months of life correlated with arm muscle area growth, a measure of lean mass (r=0.62, P=0.003), but not with growth in skinfold thickness. Early infancy weight gain was associated with poor plasma LCPUFA status at birth, and fat deposition in infancy was related to changes in placental lipid handling. Thus, neonatal fatty acid profiles may influence the trajectory of infant growth and fat and lean mass deposition.
Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses.
We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks.
Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus.
This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.
There is now a well-established link between childhood adversity (CA) and schizophrenia. Similar structural abnormalities to those found in schizophrenia including alterations in grey-matter volume have also been shown in those who experience CA.
We examined whether global estimates of cortical thickness or surface area were altered in those familial high-risk subjects who had been referred to a social worker or the Children's Panel compared to those who had not.
We found that the cortical surface area of those who were referred to the Children's Panel was significantly smaller than those who had not been referred, but cortical thickness was not significantly altered. There was also an effect of social work referral on cortical surface area but not on thickness.
Cortical surface area increases post-natally more than cortical thickness. Our findings suggest that CA can influence structural changes in the brain and it is likely to have a greater impact on cortical surface area than on cortical thickness.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
Late preterm births constitute the majority of preterm births. However, most evidence suggesting that preterm birth predicts the risk of mental disorders comes from studies on earlier preterm births. We examined if late preterm birth predicts the risks of severe mental disorders from early to late adulthood. We also studied whether adulthood mental disorders are associated with post-term birth or with being born small (SGA) or large (LGA) for gestational age, which have been previously associated with psychopathology risk in younger ages.
Of 12 597 Helsinki Birth Cohort Study participants, born 1934–1944, 664 were born late preterm, 1221 post-term, 287 SGA, and 301 LGA. The diagnoses of mental disorders were identified from national hospital discharge and cause of death registers from 1969 to 2010. In total, 1660 (13.2%) participants had severe mental disorders.
Individuals born late preterm did not differ from term-born individuals in their risk of any severe mental disorder. However, men born late preterm had a significantly increased risk of suicide. Post-term birth predicted significantly increased risks of any mental disorder in general and particularly of substance use and anxiety disorders. Individuals born SGA had significantly increased risks of any mental and substance use disorders. Women born LGA had an increased risk of psychotic disorders.
Although men born late preterm had an increased suicide risk, late preterm birth did not exert widespread effects on adult psychopathology. In contrast, the risks of severe mental disorders across adulthood were increased among individuals born SGA and individuals born post-term.
Cochlear implant surgery is increasingly being performed through a small incision because of the benefits associated with this technique, such as fewer wound complications. Efforts have been made to maximise surgical exposure in order to improve this evolving technique; this includes the development and use of new retractors. For instance, elasticated stay hooks can retract skin in a radial fashion and they are less bulky than traditional retractors. These hooks are usually attached directly to surgical drapes or to a disposable retractor ring; there are disadvantages to both of these methods.
This paper describes a technique using a laryngeal suspension bar in which the bar acts as a fixed structure to which these elasticated stay hooks can be attached.
This technique was found to be safer, cheaper and more effective for obtaining optimal surgical exposure compared with a technique whereby the stay hooks are attached directly to the drapes or to a disposable retractor ring.
White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.
Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.
We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.
WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.
Maternal experience of childhood maltreatment and maternal antenatal depression
are both associated with offspring childhood maltreatment and offspring adjustment
problems. We have investigated the relative impact of maternal childhood
maltreatment and exposure to depression in utero on offspring
maltreatment and psychopathology.
The sample included 125 families from the South London Child Development Study. A
prospective longitudinal design was used. Data on maternal childhood maltreatment,
maternal antenatal depression (36 weeks of pregnancy), offspring childhood
maltreatment (age 11 years) and offspring adolescent antisocial behaviour and
depression (ages 11 and 16 years) were obtained from parents and offspring through
Mothers who experienced childhood maltreatment were significantly more likely to
be depressed during pregnancy [odds ratio (OR) 10.00]. Offspring of mothers who
experienced only childhood maltreatment or only antenatal depression were no more
at risk of being maltreated or having psychopathology; however, offspring of
mothers who experienced both maternal childhood maltreatment and antenatal
depression were exposed to significantly greater levels of childhood maltreatment
and exhibited significantly higher levels of adolescent antisocial behaviour
compared with offspring not so exposed. Furthermore, maternal childhood
maltreatment accounted for a significant proportion of the variance in offspring
childhood maltreatment in only those offspring exposed to depression in
Maternal childhood maltreatment and maternal antenatal depression are highly
associated. The co-occurrence of both insults significantly increases the risk of
offspring adversity. The antenatal period is an optimum period to identify
vulnerable women and to provide interventions.
New findings on the maternal and placental programming of chronic disease lead to four conclusions: (1) Growth of the placental surface is polarized from the time of implantation, so that growth along the major axis, the length, is qualitatively different from growth along the minor axis, the breadth. (2) The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. This only occurs if the mother was well nourished before conception, and may have long-term costs that include hypertension. (3) The effects of placental size on long-term health are conditioned by the mother’s nutritional state, as indicated by her socio-economic status, height and body mass index. (4) The maternal–placental programming of chronic disease differs in boys and girls. Boys invest less than girls in placental growth but more readily expand the placental surface if they become undernourished in mid-late gestation. Boys are more responsive to their mothers’ current diets while girls respond more to their mothers’ lifetime nutrition and metabolism.
An international collection of 419 isolates of Salmonella agona was phage typed, biotyped and colicine typed. Of 16 recognized phage types, 15 were represented. Three phage types (I, V and XVI) accounted for 84% of all isolates, were widely distributed and may be interconvertible. Biotyping afforded little type differentiation; thus 92·6% of the isolates belonged to biotype 1 a. A rhamnose non-fermenting variant line (of biotype 5a) became established in Zaire from 1979 to 1980. A maltose late-fermenting line of biotype 1 a, isolated in Scotland in 1974, did not thereafter become established. Two Col+ lines (producing colicine I b) accounted for 45 of 68 colicinogenic isolates. The implication of type diversification and the phylogenetic significance of these findings are discussed.
Isolates of Salmonella typhimurium, recovered over a 9-month period from a child with gastroenteritis, were characterized by biotyping, phage-typing and plasmid-profile analysis. Because the data from the different methods were discrepant, it was difficult to establish whether her infection was due to a single strain that had changed character in vivo or was due to recurrent infections with different, unrelated strains. Restriction-enzyme fingerprinting of the plasmids from the different isolates provided an explanation for the initial discrepancy and highlighted a source of potential confusion in epidemiological studies.
Among the 81 cultures of Salmonella typhimurium of phage type 141 examined, 72 had been isolated from Sheffield incidents in 1984–5 and 9 were Scottish isolates from 1986–7. All of these cultures from diverse sources belonged to primary biotype 31; 79 were of full biotype 31beg and 2 anaerogenic cultures were of full biotype 31begj. This is the first known occasion on which an epidemic strain of S. typhimurium of phage type/biotype 141/31beg has been implicated in outbreaks of human or animal infection in the UK. Because previous epidemic strains of S. typhimurium of phage type 141 in the UK belonged to biotypes 1f and 9f which are phylogenetically unrelated to biotype 31beg, the likely origin of this most recent epidemic S. typhimurium strain of phage type/biotype 141/31beg is discussed.
The colour-change and lead acetate tests for fermentation of d–, l–and m–tartaric acids and citric acid used in the Kristensen scheme for biotyping Salmonella typhimurium were found to be unreliable because, whatever the conditions of culture, they gave different results in replicate tests of the same strains. Many genotypically non-fermenting strains gave inconsistent reactions due to the emergence of fermenting mutant bacilli in some of their test cultures. No reliable test was found for the fermentation of citric acid.
A ‘turbidity’ test was found to give consistent and reliable results with the three tartaric acid isomers. It demonstrated fermentation by the significantly greater amount of growth obtained in a 24 hr. culture in Oxoid peptone water with added isomer than in a control culture without isomer. Lewis & Stocker's (1971) plate-inhibition test for fermentation of m–tartrate, which identifies m–tartrate-negative strains because m–tartrate inhibits their growth on citrate- or glycerol-containing minimal medium, was found to be as reliable as, and easier to read than, the turbidity test.
Use of the turbidity test for d–and l–tartrates and the plate-inhibition test for m–tartrate in biotyping 1435 strains of S. typhimurium showed that many strains had previously been mistyped by the lead acetate test and distinguished 16 new biotypes in addition to the 22 biotypes already recognized.
A series of 2092 cultures of Salmonella typhimurium isolated from human, animal and other sources in 57 countries were differentiated into 204 phage types and 19 primary and 147 full biotypes. Different biotypes belonged to the same phage type and different phage types to the same biotype, so the combination of typing methods differentiated strains more finely than either method alone: 574 different ‘phage type/biotypes’ were distinguished in 1937 cultures belonging to the 204 recognized phage types.
The combination of biotyping with phage-typing was valuable in studying the phylogeny and spread of epidemic strains by distinguishing clones of different biotype within the same phage type and by confirming the relationship between cultures isolated from widely dispersed clones and that between cultures isolated before and after a clone had undergone variation in phage type, biotype, colicin type or antibiotic-sensitivity pattern.
A widespread outbreak of infection with S. typhimurium phage type 141 in Scotland comprised independent dissemination of three clones of different biotypes, if, 9f and 31bd. During its epidemic spread in cattle in Britain between 1962 and 1969, another strain underwent variations in phage type (type 44 to type 29), biotype (type 26a to types 26d, 26bd, 26dgi, 26dz and 26i) and antibiotic sensitivity. A group of 275 non-fimbriate, non-inositol-fermenting and non-rhamnose fermenting (FIRN) strains, particularly associated with avian infections and thought to be clonal in origin, contained 27 phage types and 22 full biotypes in the primary biotypes 29–32.