Predicting live birth, preterm and low birth weight infant after in-vitro fertilisation: a prospective study of 144018 treatment cycles

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF

Fibulin-1c regulates transforming growth factor–β activation in pulmonary tissue fibrosis

Copyright: © 2019, American Society for Clinical Investigation. Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice and stabilizes collagen formation. Here we discovered that Fbln1c was increased in the lung tissues of patients with IPF and experimental bleomycin-induced pulmonary fibrosis. Fbln1c-deficient (Fbln1c–/–) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin, and tenascin-C in collagen deposits following bleomycin challenge. In a potentially novel mechanism of fibrosis, Fbln1c bound to latent TGF-β–binding protein 1 (LTBP1) to induce TGF-β activation and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target

Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c

Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilizes collagen and other ECM proteins. The level of Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear. We show that the level of Fbln1c was increased in the lungs of mice with house dust mite (HDM)-induced chronic allergic airway disease (AAD). Genetic deletion of Fbln1c and therapeutic inhibition of Fbln1c in mice with chronic AAD reduced airway collagen deposition, and protected against AHR. Fbln1c-deficient (Fbln1c–/–) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild-type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c–/– mice with AAD also had reduced numbers of α-smooth muscle actin-positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)-5, IL-13, IL-33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL-5, IL-33 and TNF levels in lung-draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3-positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL-5 and IL-13 from co-cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium-treated controls. Our data show that Fbln1c may be a therapeutic target in chronic asthma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Pesticide Leaching from Agricultural Fields with Ridges and Furrows

In the evaluation of the risk of pesticide leaching to groundwater, the soil surface is usually assumed to be level, although important crops like potato are grown on ridges. A fraction of the water from rainfall and sprinkler irrigation may flow along the soil surface from the ridges to the furrows, thus bringing about an extra load of water and pesticide on the furrow soil. A survey of the literature reveals that surface-runoff from ridges to furrows is a well-known phenomenon but that hardly any data are available on the quantities of water and pesticide involved. On the basis of a field experiment with additional sprinkler irrigation, computer simulations were carried out with the Pesticide Emission Assessment at Regional and Local scales model for separate ridge and furrow systems in a humic sandy potato field. Breakthrough curves of bromide ion (as a tracer for water flow) and carbofuran (as example pesticide) were calculated for 1-m depth in the field. Bromide ion leached comparatively fast from the furrow system, while leaching from the ridge system was slower showing a maximum concentration of about half of that for the furrow system. Carbofuran breakthrough from the furrow system began about a month after application and increased steadily to substantial concentrations. Because the transport time of carbofuran in the ridge soil was much longer, no breakthrough occurred in the growing season. The maximum concentration of carbofuran leaching from the ridge–furrow field was computed to be a factor of six times as high as that computed for the corresponding level field. The study shows that the risk of leaching of pesticides via the furrow soil can be substantially higher than that via the corresponding level field soil

Comprehensive annotation of the Parastagonospora nodorum reference genome using next-generation genomics, transcriptomics and proteogenomics

Parastagonospora nodorum, the causal agent of Septoria nodorum blotch (SNB), is an economically important pathogen of wheat (Triticum spp.), and a model for the study of necrotrophic pathology and genome evolution. The reference P. nodorum strain SN15 was the first Dothideomycete with a published genome sequence, and has been used as the basis for comparison within and between species. Here we present an updated reference genome assembly with corrections of SNP and indel errors in the underlying genome assembly from deep resequencing data as well as extensive manual annotation of gene models using transcriptomic and proteomic sources of evidence (https://github.com/robsyme/Parastagonospora_nodorum_SN15). The updated assembly and annotation includes 8,366 genes with modified protein sequence and 866 new genes. This study shows the benefits of using a wide variety of experimental methods allied to expert curation to generate a reliable set of gene models

Conflict and user involvement in drug misuse treatment decision-making: a qualitative study

<p>Abstract</p> <p>Background</p> <p>This paper examines client/staff conflict and user involvement in drug misuse treatment decision-making.</p> <p>Methods</p> <p>Seventy-nine in-depth interviews were conducted with new treatment clients in two residential and two community drug treatment agencies. Fifty-nine of these clients were interviewed again after twelve weeks. Twenty-seven interviews were also conducted with staff, who were the keyworkers for the interviewed clients.</p> <p>Results</p> <p>Drug users did not expect, desire or prepare for conflict at treatment entry. They reported few actual conflicts within the treatment setting, but routinely discussed latent conflicts – that is, negative experiences and problematic aspects of current or previous treatment that could potentially escalate into overt disputes. Conflict resulted in a number of possible outcomes, including the premature termination of treatment; staff deciding on the appropriate outcome; the client appealing to the governance structure of the agency; brokered compromise; and staff skilfully eliciting client consent for staff decisions.</p> <p>Conclusion</p> <p>Although the implementation of user involvement in drug treatment decision-making has the potential to trigger high levels of staff-client conflict, latent conflict is more common than overt conflict and not all conflict is negative. Drug users generally want to be co-operative at treatment entry and often adopt non-confrontational forms of covert resistance to decisions about which they disagree. Staff sometimes deploy user involvement as a strategy for managing conflict and soliciting client compliance to treatment protocols. Suggestions for minimising and avoiding harmful conflict in treatment settings are given.</p