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Background Patient and Public Involvement (PPI) is a rich and valuable part of the process of planning, designing, carrying out and disseminating research. It is important to communicate PPI findings in detail so that the contributions of those involved are fully utilised and disseminated. The extended and iterative PPI process used within a neonatal randomised controlled trial related to the expression of breastmilk after very preterm birth is reported here. Methods Seven iterative stages of PPI were used. Stage 1 was informal PPI using historical interaction with parents and publicly available resources. Stage 2 was an online questionnaire open to parents of premature babies and advertised via a charity collaborator. Stage 3 was partnership with a charity collaborator. Stage 4 was a set of online panels focusing on study design and documents. Stage 5 was an interactive exercise to modify the trial intervention. Stage 6 is the presence of PPI contributors on the trial steering committee. Stage 7 is a dissemination panel. At each stage attention was paid to the diversity of participants involved, with strategies to increase the involvement of parents from under-reached groups. Results Six hundred and seventy-five participants responded at Stage 2, six parents were involved at Stage 4 and 12 parents at Stage 5. PPI contributed to the choice of study question, outcomes and produced a set of questions for future research. PPI impacted on the study design, with specific emphasis on reducing participant distress related to lactation, and reducing the burden of being involved in research at a time of significant stress. Conclusions PPI had a far-reaching influence on this neonatal randomised controlled trial during the planning and design phase, which reinforces the importance of PPI at the earliest stages of the research cycle. The online questionnaire format elicited an unexpectedly deep and broad pool of transferable insights, which will have an impact on future research focus and design in the area of lactation and prematurity. Approaches to increasing PPI involvement from under-reached populations are important and can be successful despite resource constraints.

Delivery by caesarean section has been identified as a risk factor for asthma. Meta-analyses have reported a 20% increased risk for childhood asthma or its common symptom – wheezing. However, asthma is a heterogeneous disease with distinct phenotypes portrayed as various wheezing trajectories. We sought to assess the relationship between mode of delivery at birth and three commonly identified wheezing trajectories of childhood, as well as additional asthma-related outcomes.

Background: Research into the impact of unintended pregnancy on the wellbeing of women tends to focus on pregnancies ending in either termination or lone motherhood. Unintended pregnancy is common in partnered women, but little is known about the association between unintended pregnancy and postpartum affective disorders, such as depression and anxiety in this group. Poor relationship quality and lack of social support are considered risk factors for psychological distress (PD). We examined the association between unplanned motherhood and subsequent PD in partnered women, for whom evidence is sparse, accounting for the role of relationship quality and social support. Methods: Data for 12,462 partnered mothers were drawn from the first survey of Millennium Cohort Study, completed at 9 months postpartum. Women reported whether their baby was planned, and how they felt when they discovered that they were pregnant. Pregnancy intention is categorised as “planned”, “unplanned/happy”, “unplanned/ambivalent” and “unplanned/unhappy”. PD was assessed using the modified 9-item Rutter Malaise Inventory. Social support was measured by a composite score for perceived support, and a measure of actual support from friends and family. Relationship quality was assessed using a modified Golombok-Rust Inventory of Marital State. The effect of pregnancy intention on the odds of PD at 9 months was estimated, adjusting for potential confounding factors. All analyses were weighted for response and design effects. Results: In total 32.8%(weighted) (4343/ 12462) of mothers reported an unplanned pregnancy: 23.3wt% (3087) of mothers felt happy, 3.5wt% (475) ambivalent, and 6.0wt% (781) unhappy upon discovery. Unplanned pregnancy was associated with a significantly increased odds of PD compared to planned (OR 1.73 (95%CI: 1.53, 1.95)). This was more pronounced among women who reported negative or ambivalent feelings in early pregnancy (OR 2.72 (95%CI:2.17, 3.41) and 2.56 (95%CI:1.95, 3.34), respectively), than those who reported positive feelings (OR 1.39 (95%CI:1.21, 1.60)). Adjustment for relationship quality, in particular, reduced odds of PD after unplanned pregnancy (e.g. from 2.19 (95%C: 1.74, 2.74) to 1.63 (95% CI: 1.29, 2.07 in the unplanned, unhappy group compared to the planned). Conclusions: A third of partnered mothers reported that their pregnancy was unintended, yet this group is under-researched. Unplanned motherhood was associated with increased risk of PD at 9 months postpartum, particularly among women who felt unhappy or ambivalent at the start. The roles of relationship quality and social support require further investigation, as possible means to intervene and improve maternal wellbeing.

Studies of maternal mortality have been shown to result in important improvements to women’s health. It is now recognised that in countries such as the UK, where maternal deaths are rare, the study of near-miss severe maternal morbidity provides additional information to aid disease prevention, treatment and service provision. Objectives To (1) estimate the incidence of specific near-miss morbidities; (2) assess the contribution of existing risk factors to incidence; (3) describe different interventions and their impact on outcomes and costs; (4) identify any groups in which outcomes differ; (5) investigate factors associated with maternal death; (6) compare an external confidential enquiry or a local review approach for investigating quality of care for affected women; and (7) assess the longer-term impacts. Methods Mixed quantitative and qualitative methods including primary national observational studies, database analyses, surveys and case studies overseen by a user advisory group. Setting Maternity units in all four countries of the UK. Participants Women with near-miss maternal morbidities, their partners and comparison women without severe morbidity. Main outcome measures The incidence, risk factors, management and outcomes of uterine rupture, placenta accreta, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, severe sepsis, amniotic fluid embolism and pregnancy at advanced maternal age (≥ 48 years at completion of pregnancy); factors associated with progression from severe morbidity to death; associations between severe maternal morbidity and ethnicity and socioeconomic status; lessons for care identified by local and external review; economic evaluation of interventions for management of postpartum haemorrhage (PPH); women’s experiences of near-miss maternal morbidity; long-term outcomes; and models of maternity care commissioned through experience-led and standard approaches. Results Women and their partners reported long-term impacts of near-miss maternal morbidities on their physical and mental health. Older maternal age and caesarean delivery are associated with severe maternal morbidity in both current and future pregnancies. Antibiotic prescription for pregnant or postpartum women with suspected infection does not necessarily prevent progression to severe sepsis, which may be rapidly progressive. Delay in delivery, of up to 48 hours, may be safely undertaken in women with HELLP syndrome in whom there is no fetal compromise. Uterine compression sutures are a cost-effective second-line therapy for PPH. Medical comorbidities are associated with a fivefold increase in the odds of maternal death from direct pregnancy complications. External reviews identified more specific clinical messages for care than local reviews. Experience-led commissioning may be used as a way to commission maternity services. Limitations This programme used observational studies, some with limited sample size, and the possibility of uncontrolled confounding cannot be excluded. Conclusions Implementation of the findings of this research could prevent both future severe pregnancy complications as well as improving the outcome of pregnancy for women. One of the clearest findings relates to the population of women with other medical and mental health problems in pregnancy and their risk of severe morbidity. Further research into models of pre-pregnancy, pregnancy and postnatal care is clearly needed.

The primary objective of the paper is to draw upon the experiences acquired in many parts of the world to provide an up-to-date summary of the state of the practice for source control techniques and approaches, in a sustainable development context. After a discussion of the prevailing context for urban drainage approaches, three main themes covering techniques and design criteria, institutional aspects and performance issues are discussed relative to source control implementation. The discussion is based on findings from the compilation and analysis of available literature, recently developed databases, the experience of the different members of the SOCOMA group and recent research on design methodologies that explicitly seek to better couple effective design and achievement of performance goals. The paper also discusses perceived trends in the selection, analysis, and implementation of source controls, highlighting the areas where knowledge is lacking and providing recommendations on needs for future research.

Most of the ethical debate about whether we should support human embryonic stem cell (hESC) research turns on a fundamental disagreement about how we should treat early human embryos. As it is currently done, the isolation of human embryonic stem cells (hESCs) involves dismantling the early human embryo – a process the embryo does not survive. Many people accord significant value to the human embryo (henceforth ‘embryo’) and think that embryos may not simply be used in whatever way suits our research interests. However, hESC research holds unique promise for developing therapies for currently incurable diseases, as well as for important biomedical research and drug and toxicity testing. This creates a dilemma: either one supports hESC research and accepts resulting embryo destruction, orone opposes hESC research and accepts that its potential benefits will be foregone. Of course, for some people there is no dilemma. If you believe an early human embryo is merely a collection of cells that has very little value in itself, the embryo’s moral status provides no reason to abstain from hESC research. On the other hand, if you believe that the embryo has the same moral status as a typical adult human, then isolating hESCs is equivalent to murder and is clearly unjustified. But for those who accord lesser but still significant moral status to the embryo, the dilemma is very real. A popular response to the dilemma has been to adopt some intermediate position between the dominant opposed ethical views that the moral status of the embryo always and never gives us decisive reasons to abstain from hESC research. One such intermediate position that has been widely defended and that serves as a basis for stem cell policy in many western countries, including the US under the Obama administration, is the so-called ‘discarded-created distinction’

BACKGROUND AND PURPOSE: Regional cerebral blood flow fluctuates synchronously in corresponding brain regions between the hemispheres. This synchrony implies neuronal connections between brain regions. The synchrony of blood flow changes is defined operationally as functional connectivity. Our purpose was to measure functional connectivity in patients with corpus callosal agenesis, in whom the interhemispheric connectivity is hypothetically diminished. METHODS: In three patients with agenesis of the corpus callosum, functional MR imaging was performed while patients performed text-listening and finger-tapping tasks. Functional images were also acquired while the patients performed no specific task (resting state). Regions of activation temporally correlated with the performance of the tasks were identified by cross-correlating the task data with a reference function. Voxel clusters (seed voxels) that corresponded to regions of activation in the task-activation data set were selected in the resting data set. All the voxels in the resting 3D data set that had a correlation coefficient exceeding 0.4 were identified. The number of these voxels in the ipsilateral and contralateral hemispheres was tabulated. RESULTS: In all patients, technically adequate functional MR and functional connectivity MR maps were obtained. For both tasks, activation was found in both hemispheres. For all of the seed voxels, significantly more functionally connected voxels were found in the ipsilateral hemisphere than in the contralateral hemisphere. For most seed voxels, no functionally connected voxels were found in the contralateral hemisphere. CONCLUSION: Interhemispheric functional connectivity in the motor and auditory cortices is diminished in patients with agenesis of the corpus callosum compared with that of healthy subjects.

SummaryT cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8+ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics.