Stratification of the Risk of Bipolar Disorder Recurrences in Pregnancy and Postpartum

Background Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications. Aims To explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder. Method Information was gathered retrospectively by semi-structured interview, questionnaires and case-note review from 887 women with bipolar disorder who have had children. Clinical predictors were selected using backwards stepwise logistic regression, conditional permutation random forests and reinforcement learning trees. Results Previous perinatal history of affective psychosis or depression was the most significant predictor of a perinatal recurrence (odds ratio (OR) = 8.5, 95% CI 5.04–14.82 and OR = 3.6, 95% CI 2.55–5.07 respectively) but even parous women with bipolar disorder without a previous perinatal mood episode were at risk following a subsequent pregnancy, with 7% developing postpartum psychosis. Conclusions Previous perinatal history of affective psychosis or depression is the most important predictor of perinatal recurrence in women with bipola

Weight reduction is not a major reason for improvement in rheumatoid arthritis from lacto-vegetarian, vegan or Mediterranean diets

OBJECTIVES: Several investigators have reported that clinical improvements of patients with rheumatoid arthritis (RA), from participating in therapeutic diet intervention studies, have been accompanied by loss of body weight. This has raised the question whether weight reduction per se can improve RA. In order to test this hypothesis, three previously conducted diet intervention studies, comprising 95 patients with RA, were pooled. Together with Age, Gender, and Disease Duration, change during the test period in body weight, characterised dichotomously as reduction or no reduction (dichoΔBody Weight), as well as Diet (dichotomously as ordinary diet or test diet), were the independent variables. Dependent variables were the difference (Δ) from baseline to conclusion of the study in five different disease outcome measures. ΔESR and ΔPain Score were both characterised numerically and dichotomously (improvement or no improvement). ΔAcute Phase Response, ΔPhysical Function, and ΔTender Joint Count were characterised dichotomously only. Multiple logistic regression was used to analyse associations between the independent and the disease outcome variables. RESULTS: Statistically significant correlations were found between Diet and three disease outcome variables i.e. ΔAcute-Phase Response, ΔPain Score, and ΔPhysical Function. Δ Body Weight was univariately only correlated to ΔAcute-Phase Response but not significant when diet was taken into account. CONCLUSION: Body weight reduction did not significantly contribute to the improvement in rheumatoid arthritis when eating lacto-vegetarian, vegan or Mediterranean diets

The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia

Molecular genetic analysis offers opportunities to advance our understanding of the nosological relationship between psychiatric diagnostic categories in general, and the mood and psychotic disorders in particular. Strong evidence (P=7.0 × 10−7) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar disorder (BD) has recently been reported in a meta-analysis of three genome-wide association studies of BD, including our BD sample (N=1868) studied within the Wellcome Trust Case Control Consortium. Here, we have used our UK case samples of recurrent major depression (N=1196) and schizophrenia (N=479) and UK non-psychiatric comparison groups (N=15316) to examine the spectrum of phenotypic effect of the bipolar risk allele at rs1006737. We found that the risk allele conferred increased risk for schizophrenia (P=0.034) and recurrent major depression (P=0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio ∼1.15). Our findings are evidence of some degree of overlap in the biological underpinnings of susceptibility to mental illness across the clinical spectrum of mood and psychotic disorders, and show that at least some loci can have a relatively general effect on susceptibility to diagnostic categories, as currently defined. Our findings will contribute to a better understanding of the pathogenesis of major psychiatric illness, and such knowledge should be useful in providing an etiological rationale for shaping psychiatric nosology, which is currently reliant entirely on descriptive clinical data

A Conserved Stem Loop Motif in the 5′Untranslated Region Regulates Transforming Growth Factor-β1 Translation

Transforming growth factor-β1 (TGF-β1) regulates cellular proliferation, differentiation, migration, and survival. The human TGF-β1 transcript is inherently poorly translated, and translational activation has been documented in relation to several stimuli. In this paper, we have sought to identify in cis regulatory elements within the TGF-β1 5′Untranslated Region (5′UTR). In silico analysis predicted formation of stable secondary structure in a G/C-rich element between nucleotides +77 to +106, and demonstrated that this element is highly conserved across species. Circular dichroism spectroscopy confirmed the presence of secondary structure in this region. The proximal 5′UTR was inhibitory to translation in reporter gene experiments, and mutation of the secondary structure motif increased translational efficiency. Translational regulation of TGF-β1 mRNA is linked to altered binding of YB-1 protein to its 5′UTR. Immunoprecipitation-RT-qPCR demonstrated a high basal association of YB-1 with TGF-β1 mRNA. However, mutation of the secondary structure motif did not prevent interaction of YB-1 with the 5′UTR, suggesting that YB-1 binds to this region due to its G/C-rich composition, rather than a specific, sequence-dependent, binding site. These data identify a highly conserved element within the TGF-β1 5′UTR that forms stable secondary structure, and is responsible for the inherent low translation efficiency of this cytokine

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

In search of the ‘great horse’: A zooarchaeological assessment of horses from England (AD 300-1650)

Popular culture presents a deep-rooted perception of medieval warhorses as massive and powerful mounts, but medieval textual and iconographic evidence remains highly debated. Furthermore, identifying warhorses in the zooarchaeological record is challenging due to both a paucity of horse remains relative to other domesticates, and the tendency of researchers to focus on osteological size, which makes it difficult to reconstruct in-life usage of horses and activity related changes. This paper presents the largest zooarchaeological dataset of English horse bones (n = 1964) from 171 unique archaeological sites dating between AD 300 and 1650. Using this dataset alongside a modern comparative sample of known equids (n = 490), we examine trends in size and shape to explore how the skeletal conformation of horses changed through time and reflected their domestic, elite and military roles. In addition to evidencing the generally small stature of medieval horses relative to both earlier and later periods, we demonstrate the importance of accurately exploring the shape of skeletal elements to describe the morphological characteristics of domestic animals. Furthermore, we highlight the need to examine shape variation in the context of entheseal changes and biomechanics to address questions of functional morphology and detect possible markers of artificial selection on past horses

The genome of the Trinidadian guppy, Poecilia reticulata, and variation in the Guanapo population

For over a century, the live bearing guppy, Poecilia reticulata, has been used to study sexual selection as well as local adaptation. Natural guppy populations differ in many traits that are of intuitively adaptive significance such as ornamentation, age at maturity, brood size and body shape. Water depth, light supply, food resources and predation regime shape these traits, and barrier waterfalls often separate contrasting environments in the same river. We have assembled and annotated the genome of an inbred single female from a high-preda- tion site in the Guanapo drainage. The final assembly comprises 731.6 Mb with a scaffold N50 of 5.3 MB. Scaffolds were mapped to linkage groups, placing 95% of the genome assembly on the 22 autosomes and the X-chromosome. To investigate genetic variation in the population used for the genome assembly, we sequenced 10 wild caught male individu- als. The identified 5 million SNPs correspond to an average nucleotide diversity (π) of 0.0025. The genome assembly and SNP map provide a rich resource for investigating adap- tation to different predation regimes. In addition, comparisons with the genomes of other Poeciliid species, which differ greatly in mechanisms of sex determination and maternal resource allocation, as well as comparisons to other teleost genera can begin to reveal how live bearing evolved in teleost fish

Effect of the one-child policy on influenza transmission in China: a stochastic transmission model

published_or_final_versio

Patterns of Gene Flow Define Species of Thermophilic Archaea

A genomic view of speciation in Archaea shows higher rates of gene flow within coexisting microbial species than between them