Perinatal or neonatal mortality among women who intend at the onset of labour to give birth at home compared to women of low obstetrical risk who intend to give birth in hospital: A systematic review and meta-analyses

Background: More women are choosing to birth at home in well-resourced countries. Concerns persist that out-of-hospital birth contributes to higher perinatal and neonatal mortality. This systematic review and meta-analyses determines if risk of fetal or neonatal loss differs among low-risk women who begin labour intending to give birth at home compared to low-risk women intending to give birth in hospital. Methods: In April 2018 we searched five databases from 1990 onward and used R to obtain pooled estimates of effect. We stratified by study design, study settings and parity. The primary outcome is any perinatal or neonatal death after the onset of labour. The study protocol is peer-reviewed, published and registered (PROSPERO No.CRD42013004046). Findings: We identified 14 studies eligible for meta-analysis including ~ 500,000 intended home births. Among nulliparous women intending a home birth in settings where midwives attending home birth are well-integrated in health services, the odds ratio (OR) of perinatal or neonatal mortality compared to those intending hospital birth was 1.07 (95% Confidence Interval [CI], 0.70 to 1.65); and in less integrated settings 3.17 (95% CI, 0.73 to 13.76). Among multiparous women intending a home birth in well-integrated settings, the estimated OR compared to those intending a hospital birth was 1.08 (95% CI, 0.84 to 1.38); and in less integrated settings was 1.58 (95% CI, 0.50 to 5.03). Interpretation: The risk of perinatal or neonatal mortality was not different when birth was intended at home or in hospital. Funding: Partial funding: Association of Ontario Midwives open peer reviewed grant. Research in Context: Evidence before this study Although there is increasing acceptance for intended home birth as a choice for birthing women, controversy about its safety persists. The varying responses of obstetrical societies to intended home birth provide evidence of contrasting views. A Cochrane review of randomised controlled trials addressing this topic included one small trial and noted that in the absence of adequately sized randomised controlled trials on the topic of intended home compared to intended hospital birth, a peer reviewed protocol be published to guide a systematic review and meta-analysis including observational studies. Reviews to date have been limited by design or methodological issues and none has used a protocol published a priori.Added value of this study Individual studies are underpowered to detect small but potentially important differences in rare outcomes. This study uses a published peer-reviewed protocol and is the largest and most comprehensive meta-analysis comparing outcomes of intended home and hospital birth. We take study design, parity and jurisdictional support for home birth into account. Our study provides much needed information to policy makers, care providers and women and families when planning for birth.Implications of all the available evidence Women who are low risk and who intend to give birth at home do not appear to have a different risk of fetal or neonatal loss compared to a population of similarly low risk women intending to give birth in hospital

Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies

Action planning and the timescale of evidence accumulation

Perceptual decisions are based on the temporal integration of sensory evidence for different states of the outside world. The timescale of this integration process varies widely across behavioral contexts and individuals, and it is diagnostic for the underlying neural mechanisms. In many situations, the decision-maker knows the required mapping between perceptual evidence and motor response (henceforth termed “sensory-motor contingency”) before decision formation. Here, the integrated evidence can be directly translated into a motor plan and, indeed, neural signatures of the integration process are evident as build-up activity in premotor brain regions. In other situations, however, the sensory-motor contingencies are unknown at the time of decision formation. We used behavioral psychophysics and computational modeling to test if knowledge about sensory-motor contingencies affects the timescale of perceptual evidence integration. We asked human observers to perform the same motion discrimination task, with or without trial-to-trial variations of the mapping between perceptual choice and motor response. When the mapping varied, it was either instructed before or after the stimulus presentation. We quantified the timescale of evidence integration under these different sensory-motor mapping conditions by means of two approaches. First, we analyzed subjects’ discrimination threshold as a function of stimulus duration. Second, we fitted a dynamical decision-making model to subjects’ choice behavior. The results from both approaches indicated that observers (i) integrated motion information for several hundred ms, (ii) used a shorter than optimal integration timescale, and (iii) used the same integration timescale under all sensory-motor mappings. We conclude that the mechanisms limiting the timescale of perceptual decisions are largely independent from long-term learning (under fixed mapping) or rapid acquisition (under variable mapping) of sensory-motor contingencies. This conclusion has implications for neurophysiological and neuroimaging studies of perceptual decision-making

Peptide Bβ15-42 Preserves Endothelial Barrier Function in Shock

Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn−/− mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock

Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion