Intervention Now to Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, and qualitative and realist synthesis of implementation factors and user engagement.

BACKGROUND: Unintended repeat conceptions can result in emotional, psychological and educational harm to young women, often with enduring implications for their life chances. This study aimed to identify which young women are at the greatest risk of repeat unintended pregnancies; which interventions are effective and cost-effective; and what are the barriers to and facilitators for the uptake of these interventions. METHODS: We conducted a mixed-methods systematic review which included meta-analysis, framework synthesis and application of realist principles, with stakeholder input and service user feedback to address this. We searched 20 electronic databases, including MEDLINE, Excerpta Medica database, Applied Social Sciences Index and Abstracts and Research Papers in Economics, to cover a broad range of health, social science, health economics and grey literature sources. Searches were conducted between May 2013 and June 2014 and updated in August 2015. RESULTS: Twelve randomised controlled trials (RCTs), two quasi-RCTs, 10 qualitative studies and 53 other quantitative studies were identified. The RCTs evaluated psychosocial interventions and an emergency contraception programme. The primary outcome was repeat conception rate: the event rate was 132 of 308 (43%) in the intervention group versus 140 of 289 (48%) for the control group, with a non-significant risk ratio (RR) of 0.92 [95% confidence interval (CI) 0.78-1.08]. Four studies reported subsequent birth rates: 29 of 237 (12%) events for the intervention arm versus 46 out of 224 (21%) for the control arm, with an RR of 0.60 (95% CI 0.39-0.93). Many repeat conceptions occurred in the context of poverty, low expectations and aspirations and negligible opportunities. Qualitative and realist evidence highlighted the importance of context, motivation, future planning and giving young women a central and active role in the development of new interventions. CONCLUSIONS: Little or no evidence for the effectiveness or cost-effectiveness of any of the interventions to reduce repeat pregnancy in young women was found. Qualitative and realist evidence helped to explain gaps in intervention design that should be addressed. More theory-based, rigorously evaluated programmes need to be developed to reduce unintended repeat pregnancy in young women. TRIAL REGISTRATION: PROSPERO, CRD42012003168 . Cochrane registration number: i = fertility/0068

MAMPs signatures, synergy, size and charge: influences on perception or mobility and host defence responses.

Triggering of defences by microbes has mainly been investigated using single elicitors or microbe-associated molecular patterns (MAMPs), but MAMPs are released in planta as complex mixtures together with endogenous oligogalacturonan (OGA) elicitor. We investigated the early responses in Arabidopsis of calcium influx and oxidative burst induced by non-saturating concentrations of bacterial MAMPs, used singly and in combination: flagellin peptide (flg22), elongation factor peptide (elf18), peptidoglycan (PGN) and component muropeptides, lipo-oligosaccharide (LOS) and core oligosaccharides. This revealed that some MAMPs have additive (e.g. flg22 with elf18) and even synergistic (flg22 and LOS) effects, whereas others mutually interfere (flg22 with OGA). OGA suppression of flg22-induced defences was not a result of the interference with the binding of flg22 to its receptor flagellin-sensitive 2 (FLS2). MAMPs induce different calcium influx signatures, but these are concentration dependent and unlikely to explain the differential induction of defence genes [pathogenesis-related gene 1 (PR1), plant defensin gene 1.2 (PDF1.2) and phenylalanine ammonia lyase gene 1 (PAL1)] by flg22, elf18 and OGA. The peptide MAMPs are potent elicitors at subnanomolar levels, whereas PGN and LOS at high concentrations induce low and late host responses. This difference might be a result of the restricted access by plant cell walls of MAMPs to their putative cellular receptors. flg22 is restricted by ionic effects, yet rapidly permeates a cell wall matrix, whereas LOS, which forms supramolecular aggregates, is severely constrained, presumably by molecular sieving. Thus, MAMPs can interact with each other, whether directly or indirectly, and with the host wall matrix. These phenomena, which have not been considered in detail previously, are likely to influence the speed, magnitude, versatility and composition of plant defences