To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.
A total economic merit index (Pasture Profit Index, PPI) for perennial ryegrass variety selection was developed to rank perennial ryegrass varieties (Lolium perenne L.) based on their economic potential for grass-based ruminant production systems. The key traits of importance identified were: spring, mid-season (April 11–August 10) and autumn dry matter (DM) yield, first and second cut silage DM yield, grass quality April to July (inclusive) and sward persistency. Variety persistency was quantified by determining the ground score (GS) change across years, which was associated with a yield threshold which triggered sward replacement. Each one-unit decline in GS was associated with a 1683 kg loss in DM yield. Data generated in the Irish recommended list trials for value for cultivation and use were analysed to quantify the relative performance of each variety for each of the aforementioned traits. A previously developed methodology to generate economic values was used with updated price assumptions to develop economic values, which were applied to the analysed performance data of individual varieties. These data were used to estimate the total economic merit of each variety. Thirty-nine varieties were ranked on total economic merit with the highest performing variety (Cv111) generating €213 per ha/year compared with Cv201, which was the lowest ranking variety generating −€31 per ha/year. Use of the PPI provides information to end users in relation to the economic merit of one variety over another, facilitating a more informed decision-making process at farm level.
Personalized or precision medicine is predicated on the assumption that the average response to treatment is not necessarily representative of the response of each individual. A commitment to personalized medicine demands an effort to bring evidence-based medicine and personalized medicine closer together. The use of relatively homogeneous groups, defined using a priori criteria, may constitute a promising initial step for developing more accurate risk-prediction models with which to advance the development of personalized evidence-based medicine approaches to heterogeneous syndromes such as schizophrenia. However, this can lead to a paradoxical situation in the field of psychiatry. Since there has been a tendency to loosely define psychiatric disorders as ones without a known aetiology, the discovery of an aetiology for psychiatric syndromes (e.g. 22q11.2 deletion syndrome in some cases of schizophrenia), while offering a path toward more precise treatments, may also lead to their reclassification away from psychiatry. We contend that psychiatric disorders with a known aetiology should not be removed from the field of psychiatry. This knowledge should be used instead to guide treatment, inasmuch as psychotherapies, pharmacotherapies and other treatments can all be valid approaches to mental disorders. The translation of the personalized clinical approach inherent to psychiatry into evidence-based precision medicine can lead to the development of novel treatment options for mental disorders and improve outcomes.
The objective of this experiment was to compare the effects of two concentrate feeding strategies offered with a grass silage and maize silage diet on the dry matter (DM) intake, milk production (MP) and estimated energy balance of autumn calved dairy cows. Over a 2-year period, 180 autumn calving Holstein Friesian cows were examined. Within year, cows were blocked into three MP sub-groups (n=9) (high (HMP), medium (MMP) and low (LMP)) based on the average MP data from weeks 3 and 4 of lactation. Within a block cows were randomly assigned to one of two treatments (n=54), flat rate (FR) concentrate feeding or feed to yield (FY) based on MP sub-group. Cows on the FR treatment were offered a fixed rate of concentrate (5.5 kg DM/cow per day) irrespective of MP sub-group. In the FY treatment HMP, MMP and LMP cows were allocated 7.3, 5.5 and 3.7 kg DM of concentrate, respectively. The mean concentrate offered to the FR and FY treatments was the same. On the FR treatment there was no significant difference in total dry matter intake (TDMI, 17.3 kg) between MP sub-groups. In the FY treatment, however, the TDMI of HMP-FY was 2.2 kg greater than MMP-FY, and 4.5 kg greater than LMP-FY (15.2 kg DM). The milk yield of LMP-FR was 3.5 kg less than the mean of the HMP-FR and MMP-FR treatments (24.5 kg). The milk yield of the HMP-FY treatment was 3.6 and 7.9 kg greater than the MMP-FY and LMP-FY treatments, respectively. The difference in MP between the HMP sub-groups was 2.6 kg, which translates to a response of 1.4 kg of milk per additional 1 kg of concentrate offered. There was no significant difference in MP between the two LMP sub-groups; however, MP increased 0.8 kg per additional 1 kg of concentrate offered between cows on the LMP-FR and LMP-FY treatments. The estimated energy balance was positive for cows on the LMP-FR treatment, but negative for cows on the other treatments. The experiment highlights the variation within a herd in MP response to concentrate, as cows with a lower MP potential are less responsive to additional energy input than cows with a greater MP potential. Cows with a greater MP capacity did not substitute additional concentrate for the basal forage, which indicates an additional demand for energy based on ability of individual cows to produce milk.
To describe adherence with infant feeding and complementary feeding guidelines.
Prospective study of infant feeding and complementary feeding practices were collected as part of the Cork BASELINE Birth Cohort Study.
Data are described for the 823 infants for whom a diary was completed.
Breast-feeding was initiated in 81 % of infants, and 34 %, 14 % and 1 % of infants were exclusively breast-fed at hospital discharge, 2 and 6 months, respectively. Stage one infant formula decreased from 71 % at 2 months to 13 % at 12 months. The majority of infants (79 %) were introduced to solids between 17 and 26 weeks and 18 % were given solid foods before 17 weeks. Mothers of infants who commenced complementary feeding prior to 17 weeks were younger (29·8 v. 31·5 years; P<0·001) and more likely to smoke (18 v. 8 %; P=0·004). The first food was usually baby rice (69 %), infant breakfast cereals (14 %) or fruit/vegetables (14 %). Meals were generally home-made (49 %), cereal-based (35 %), manufactured (10 %), dairy (3 %) and dessert-based (3 %). The median gap between the first–second, second–third, third–fourth and fourth–fifth new foods was 4, 2, 2 and 2 d, respectively.
We present the largest prospective cohort study to date on early infant feeding in Ireland. The rate of breast-feeding is low by international norms. Most mothers introduce complementary foods between 4 and 6 months with lengthy gaps between each new food/food product. There is a high prevalence of exposure to infant breakfast cereals, which are composite foods, among the first foods introduced.
A number of copy number variants (CNVs) have been suggested as
susceptibility factors for schizophrenia. For some of these the data
remain equivocal, and the frequency in individuals with schizophrenia is
To determine the contribution of CNVs at 15 schizophrenia-associated loci
(a) using a large new data-set of patients with schizophrenia
(n = 6882) and controls (n = 6316),
and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
We found higher rates in participants with schizophrenia than in controls
for 13 of the 15 previously implicated CNVs. Six were nominally
significantly associated (P<0.05) in this new
data-set: deletions at 1q21.1, NRXN1, 15q11.2 and
22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi
Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were
of maternal origin. When combined with published data, 11 of the 15 loci
showed highly significant evidence for association with schizophrenia
We strengthen the support for the majority of the previously implicated
CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9%
of controls carry a large, detectable CNV at one of these loci. Routine
CNV screening may be clinically appropriate given the high rate of known
deleterious mutations in the disorder and the comorbidity associated with
these heritable mutations.
Despite the large budgets spent annually on astronomical research equipment such as telescopes, instruments, and supercomputers, the general trend is to analyze and view the resulting datasets using small, two-dimensional displays. We report here on alternative advanced image displays, with an emphasis on displays that we have constructed, including stereoscopic projection, multiple projector tiled displays, and a digital dome. These displays can provide astronomers with new ways of exploring the terabyte and petabyte datasets that are now regularly being produced from all-sky surveys, high-resolution computer simulations, and Virtual Observatory projects. We also present a summary of the Advanced Image Displays for Astronomy (AIDA) survey which we conducted from 2005 March–May, in order to raise some issues pertinent to the current and future level of use of advanced image displays.
Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for schizophrenia and overlapping susceptibility for bipolar disorder.
To test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder.
Using a polygenic score analysis to test whether schizophrenia polygenic risk alleles, en masse, significantly discriminate between individuals with bipolar disorder with and without psychotic features. The primary sample included 1829 participants with bipolar disorder and the replication sample comprised 506 people with bipolar disorder.
The subset of participants with Research Diagnostic Criteria schizoaffective bipolar disorder (n = 277) were significantly discriminated from the remaining participants with bipolar disorder (n = 1552) in both the primary (P = 0.00059) and the replication data-sets (P = 0.0070). In contrast, those with psychotic bipolar disorder as a whole were not significantly different from those with non-psychotic bipolar disorder in either data-set.
Genetic susceptibility influences at least two major domains of psychopathological variation in the schizophrenia–bipolar disorder clinical spectrum: one that relates to expression of a ‘bipolar disorder-like’ phenotype and one that is associated with expression of ‘schizophrenia-like’ psychotic symptoms.
The objective of the current study was to develop, validate and describe a decision support system (DSS) to evaluate cull dairy cow finishing strategies. The DSS was developed within a Microsoft Excel framework. The purpose of a DSS is to assist the process of making accurate and repeatable calculations, assisting the decision on which cull cow finishing strategy is most profitable under individual farm circumstances. The model was based on data from two evaluation experiments including eight finishing strategies in total: ad libitum grass silage (GS); GS+3 kg concentrate (GS+3); GS+6 kg concentrate (GS+6); GS+9 kg concentrate (GS+9); ad libitum grass silage prior to ad libitum spring grass (GS+G); 0·75 grass silage and 0·25 straw prior to ad libitum spring grass (GS+S) and finally grass silage plus 6 kg concentrate dry matter (DM)/cow/day and milked twice daily prior to ad libitum spring grass (EXTLAC). Stochastic budgeting was included in the model to account for variability in key input and output variables on the overall profitability of various finishing strategies. The stochastic input and output variables included in the model were initial carcass value, feed strategy, concentrate cost and final carcass value. Net profit per cow was selected as the output distribution. The mean net profit per cow with the GS, GS+3, GS+6, GS+9, GS+G, GS+S and EXTLAC was €85·3, €73·7, €95·6, €58·5, €158·8 and €186·8 and €283·0, respectively. Profitability for the EXTLAC strategy was stochastically dominant to all other strategies evaluated meaning a higher level of profit and a lower level of risk is associated with the EXTLAC strategy. The optimal strategy of cull cow beef production depends greatly on the prevailing economic environment, purchase and sale price, milk price, feed costs, housing and labour.
Childbirth has been linked to postpartum impairment. However, controversy exists regarding the onset and prevalence of post-traumatic stress disorder (PTSD) after childbirth, with seminal studies being limited by methodological issues. This longitudinal prospective study examined the prevalence of PTSD following childbirth in a large sample while controlling for pre-existing PTSD and affective symptomatology.
Pregnant women in their third trimester were recruited over a 12-month period and interviewed to identify PTSD and anxiety and depressive symptoms during the last trimester of pregnancy, 4–6 weeks postpartum, 12 weeks postpartum and 24 weeks postpartum.
Of the 1067 women approached, 933 were recruited into the study. In total, 866 (93%) were retained to 4–6 weeks, 826 (89%) were retained to 12 weeks and 776 (83%) were retained to 24 weeks. Results indicated that, uncontrolled, 3.6% of women met PTSD criteria at 4–6 weeks postpartum, 6.3% at 12 weeks postpartum and 5.8% at 24 weeks postpartum. When controlling for PTSD and partial PTSD due to previous traumatic events as well as clinically significant anxiety and depression during pregnancy, PTSD rates were less at 1.2% at 4–6 weeks, 3.1% at 12 weeks and 3.1% at 24 weeks postpartum.
This is the first study to demonstrate the occurrence of full criteria PTSD resulting from childbirth after controlling for pre-existing PTSD and partial PTSD and clinically significant depression and anxiety in pregnancy. The findings indicate that PTSD can result from a traumatic birth experience, though this is not the normative response.
Psychiatric phenotypes are currently defined according to sets of
descriptive criteria. Although many of these phenotypes are heritable, it
would be useful to know whether any of the various diagnostic categories
in current use identify cases that are particularly helpful for
To use genome-wide genetic association data to explore the relative
genetic utility of seven different descriptive operational diagnostic
categories relevant to bipolar illness within a large UK case–control
bipolar disorder sample.
We analysed our previously published Wellcome Trust Case Control
Consortium (WTCCC) bipolar disorder genome-wide association data-set,
comprising 1868 individuals with bipolar disorder and 2938 controls
genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met
stringent criteria for genotype quality. For each SNP we performed a test
of association (bipolar disorder group v. control group) and used the
number of associated independent SNPs statistically significant at
P<0.00001 as a metric for the overall genetic
signal in the sample. We next compared this metric with that obtained
using each of seven diagnostic subsets of the group with bipolar
disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic
disorder; bipolar II disorder; schizoaffective disorder, bipolar type;
DSM–IV: bipolar I disorder; bipolar II disorder; schizoaffective
disorder, bipolar type.
The RDC schizoaffective disorder, bipolar type (v.
controls) stood out from the other diagnostic subsets as having a
significant excess of independent association signals
(P<0.003) compared with that expected in samples of
the same size selected randomly from the total bipolar disorder group
data-set. The strongest association in this subset of participants with
bipolar disorder was at rs4818065 (P = 2.42 ×
10–7). Biological systems implicated included gamma
amniobutyric acid (GABA)A receptors. Genes having at least one
associated polymorphism at P<10–4 included
B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and
Our findings show that individuals with broadly defined bipolar
schizoaffective features have either a particularly strong genetic
contribution or that, as a group, are genetically more homogeneous than
the other phenotypes tested. The results point to the importance of using
diagnostic approaches that recognise this group of individuals. Our
approach can be applied to similar data-sets for other psychiatric and