A sequence analysis of patterns in self-harm in young people with and without experience of being looked-after in care

Objectives: Young people in the public care system (‘looked-after’ young people) have high levels of self-harm. Design: This paper reports the first detailed study of factors leading to self-harm over time in looked-after young people in England, using sequence analyses of the Card Sort Task for Self-harm (CaTS). Methods: Young people in care (looked-after group: n = 24; 14-21 years) and young people who had never been in care (contrast group: n = 21; 13-21 years) completed the CaTS, describing sequences of factors leading to their first and most recent episodes of self-harm. Lag sequential analysis determined patterns of significant transitions between factors (thoughts, feelings, behaviours, events) leading to self-harm across six months. Results: Young people in care reported feeling better immediately following their first episode of self-harm. However, fearlessness of death, impulsivity and access to means were reported most proximal to recent self-harm. Although difficult negative emotions were salient to self-harm sequences in both groups, young people with no experience of being in care reported a greater range of negative emotions and transitions between them. For the contrast group, feelings of depression and sadness were a significant starting point of the self-harm sequence six months prior to most recent self-harm. Conclusions: Sequences of factors leading to self-harm can change and evolve over time, so regular monitoring and assessment of each self-harm episode is needed. Support around easing and dealing with emotional distress is required. Restricting access to means to carry out potentially fatal self-harm attempts, particularly for the young persons with experience of being in care, is recommended

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel

From segment to somite: segmentation to epithelialization analyzed within quantitative frameworks

One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization

The influence of the representation of collagen fibre organisation on the cartilage contact mechanics of the hip joint

The aim of this study was to develop a finite element (FE) hip model with subject-specific geometry and biphasic cartilage properties. Different levels of detail in the representation of fibre reinforcement were considered to evaluate the feasibility to simplify the complex depth-dependent fibre pattern in the native hip joint. A FE model of a cadaveric hip with subject-specific geometry was constructed through micro-computed-tomography (µCT) imaging. The cartilage was assumed to be biphasic and fibre-reinforced with different levels of detail in the fibre representation. Simulations were performed for heel-strike, mid-stance and toe-off during walking and one-leg-stance over 1500s. It was found that the required level of detail in fibre representation depends on the parameter of interest. The contact stress of the native hip joint could be realistically predicted by simplifying the fibre representation to being orthogonally reinforced across the whole thickness. To predict the fluid pressure, depth-dependent fibre organisation is needed but specific split-line pattern on the surface of cartilage is not necessary. Both depth-dependent and specific surface fibre orientations are required to simulate the strains

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Inter-Homolog Crossing-Over and Synapsis in Arabidopsis Meiosis Are Dependent on the Chromosome Axis Protein AtASY3

In this study we have analysed AtASY3, a coiled-coil domain protein that is required for normal meiosis in Arabidopsis. Analysis of an Atasy3-1 mutant reveals that loss of the protein compromises chromosome axis formation and results in reduced numbers of meiotic crossovers (COs). Although the frequency of DNA double-strand breaks (DSBs) appears moderately reduced in Atasy3-1, the main recombination defect is a reduction in the formation of COs. Immunolocalization studies in wild-type meiocytes indicate that the HORMA protein AtASY1, which is related to Hop1 in budding yeast, forms hyper-abundant domains along the chromosomes that are spatially associated with DSBs and early recombination pathway proteins. Loss of AtASY3 disrupts the axial organization of AtASY1. Furthermore we show that the AtASY3 and AtASY1 homologs BoASY3 and BoASY1, from the closely related species Brassica oleracea, are co-immunoprecipitated from meiocyte extracts and that AtASY3 interacts with AtASY1 via residues in its predicted coiled-coil domain. Together our results suggest that AtASY3 is a functional homolog of Red1. Since studies in budding yeast indicate that Red1 and Hop1 play a key role in establishing a bias to favor inter-homolog recombination (IHR), we propose that AtASY3 and AtASY1 may have a similar role in Arabidopsis. Loss of AtASY3 also disrupts synaptonemal complex (SC) formation. In Atasy3-1 the transverse filament protein AtZYP1 forms small patches rather than a continuous SC. The few AtMLH1 foci that remain in Atasy3-1 are found in association with the AtZYP1 patches. This is sufficient to prevent the ectopic recombination observed in the absence of AtZYP1, thus emphasizing that in addition to its structural role the protein is important for CO formation

Measurement of the Generalized Polarizabilities of the Proton in Virtual Compton Scattering

We propose to conduct a measurement of the Virtual Compton Scattering reaction in Hall C that will allow the precise extraction of the two scalar Generalized Polarizabilities (GPs) of the proton in the region of $Q^2=0.05~(GeV/c)^2$ to $Q^2=0.50~(GeV/c)^2$. The Generalized Polarizabilities are fundamental properties of the proton, that characterize the system's response to an external electromagnetic (EM) field. They describe how easily the charge and magnetization distributions inside the system are distorted by the EM field, mapping out the resulting deformation of the densities in the proton. As such, they reveal unique information regarding the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents together. Recent measurements of the proton GPs have challenged the theoretical predictions, particularly in regard to the electric polarizability. The magnetic GP, on the other hand, can provide valuable insight to the competing paramagnetic and diamagnetic contributions in the proton, but it is poorly known within the region where the interplay of these processes is very dynamic and rapidly changing.The unique capabilities of Hall C, namely the high resolution of the spectrometers combined with the ability to place the spectrometers in small angles, will allow to pin down the dynamic signature of the GPs through high precision measurements combined with a fine mapping as a function of $Q^2$. The experimental setup utilizes standard Hall C equipment, as was previously employed in the VCS-I (E12-15-001) experiment, namely the HMS and SHMS spectrometers and a 10 cm liquid hydrogen target. A total of 59 days of unpolarized 75 $\mu A$ electron beam with energy of 1100 MeV (6 days) and 2200 MeV (53 days) is requested for this experiment