Recognising uncertainty: an integrated framework for palliative care in perinatal medicine.

In perinatal medicine, the number of babies with life-limiting or life-threatening conditions is increasing and the benefits of providing palliative care with a holistic, interdisciplinary approach are well documented. It can be particularly challenging, however, to integrate palliative care into routine care where there exists uncertainty about a baby's diagnosis or potential outcome.This framework, developed collaboratively by the British Association of Perinatal Medicine (BAPM) and the Association of Paediatric Palliative Medicine (APPM), offers supportive guidance for all healthcare professionals working in perinatal medicine across antenatal and neonatal services.

Experience of the first adult-focussed undiagnosed disease program in Australia (AHA-UDP): solving rare and puzzling genetic disorders is ageless.

Background: Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing for children with rare diseases in many centres, but there remains a service gap for adults. The Austin Health Adult Undiagnosed Disease Program (AHA-UDP) was designed to complement existing UDP programs that focus on paediatric rare diseases and address an area of unmet diagnostic need for adults with undiagnosed rare conditions in Victoria, Australia. It was conducted at a large Victorian hospital to demonstrate the benefits of bringing genomic techniques currently used predominantly in a research setting into hospital clinical practice, and identify the benefits of enrolling adults with undiagnosed rare diseases into a UDP program.

Fetal dose assessment in a pregnant patient with brain tumor: A comparative study of proton PBS and 3DCRT/VMAT radiation therapy techniques.

Purpose: The treatment of brain tumors in pregnant patients poses challenges, as the out-of-field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre-treatment study that compared fetal dose exposure between intensity-modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment.

Stepping back or stepping in: A qualitative investigation of self-distanced versus self-immersed stressor reflections with competitive swimmers.

High performance sport consists of stressor events which can disrupt an athletes' functioning and negatively influence performance. The way in which one reflects upon stressor events and develops insights regarding how they coped is essential to overcoming similar experiences in the future. We conducted a pilot randomised controlled trial with a qualitative analysis to explore the coping insights among 48 highly trained/national level swimmers in the lead up to major swimming competitions, who reflected on stressor events from self-distanced or self-immersed perspectives over a 3-week period.

Hypothesis: evidence that the PRS gene products of Saccharomyces cerevisiae support both PRPP synthesis and maintenance of cell wall integrity.

The gene products of PRS1-PRS5 in Saccharomyces cerevisiae are responsible for the production of PRPP (5-phospho-D-ribosyl-α-1-pyrophosphate). However, it has been demonstrated that they are also involved in the cell wall integrity (CWI) signalling pathway as shown by protein-protein interactions (PPIs) with, for example Slt2, the MAP kinase of the CWI pathway. The following databases: SGD, BioGRID and Hit Predict, which collate PPIs from various research papers, have been scrutinized for evidence of PPIs between Prs1-Prs5 and components of the CWI pathway.

Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.

Aim: Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue.

Stressor reflections, sleep, and psychological well-being: A pre-registered experimental test of self-distanced versus self-immersed reflections.

Evidence supports the effectiveness of cuing people to analyse negative autobiographical experiences from self-distanced rather than self-immersed perspectives. However, the evidence on which this expectation resides is limited largely to static snapshots of mean levels of cognitive and emotional factors. Via a pre-registered, randomised controlled trial (N = 257), we examined the differential effectiveness of self-distanced relative to self-immersed reflections on mean levels and within-person variability of sleep duration and quality as well as psychological well-being over a 5-day working week.

The effectiveness of self-distanced versus self-immersed reflections among adults: Systematic review and meta-analysis of experimental studies.

Stressor events can be highly emotional and disruptive to our functioning, yet they also present opportunities for learning and growth via self-reflections. Self-distanced reflections in which one reasons about target events in ways that maximise their removal of the current self from the experiential reality are said to facilitate this reflective process. We tested the expectation that self-distanced reflections offer an advantage over self-immersed vistas via a pre-registered systematic review of seven electronic databases (Scopus, Medline, Web of Science, PsycInfo, CINAHL Plus, Embase, and ProQuest Dissertations and Theses Global) to identify experimental tests with adults aged 18-65 years where the focus of the reflection was a stressor or adverse event that participants had already experienced.

Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial.

Background: 2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth.

Methods: This stepped wedge, cluster-randomised trial was done in the UK and Ireland.

Honey bee neurogenomic responses to affiliative and agonistic social interactions.

Social interactions can be divided into two categories, affiliative and agonistic. How neurogenomic responses reflect these opposing valences is a central question in the biological embedding of experience. To address this question, we exposed honey bees to a queen larva, which evokes nursing, an affiliative alloparenting interaction, and measured the transcriptomic response of the mushroom body brain region at different times after exposure.

Creating a mouse model resistant to induced ischemic stroke and cardiovascular damage.

Vascular prostanoids, isomerized from an intermediate prostaglandin (PG), H, produced by cyclooxygenase (COX), exert various effects on the vascular system, both protective and destructive. During endothelial dysfunction, vascular protector prostacyclin/prostaglandin I (PGI) is decreased, while inflammatory PGE and thrombotic TXA are increased. Therefore, our research aim was to reverse the event by controlling PGH metabolism by generating an in vivo model via enzymatic engineering of COX-1 and prostacyclin synthase (PGIS).

Can promoting awareness of fetal movements and focusing interventions reduce fetal mortality? A stepped-wedge cluster randomised trial (AFFIRM).

Background: In 2013, the stillbirth rate in the UK was 4.2 per 1000 live births, ranking 24th out of 49 high-income countries, with an annual rate of reduction of only 1.4% per year.

Behavioral, transcriptomic and epigenetic responses to social challenge in honey bees.

Understanding how social experiences are represented in the brain and shape future responses is a major challenge in the study of behavior. We addressed this problem by studying behavioral, transcriptomic and epigenetic responses to intrusion in honey bees. Previous research showed that initial exposure to an intruder provokes an immediate attack; we now show that this also leads to longer-term changes in behavior in the response to a second intruder, with increases in the probability of responding aggressively and the intensity of aggression lasting 2 and 1 h, respectively.

The key residue within the second extracellular loop of human EP3 involved in selectively turning down PGE- and retaining PGE-mediated signaling in live cells.

Key residues and binding mechanisms of PGE and PGE on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE and PGE docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site.

A survey of ancient conserved non-coding elements in the PAX6 locus reveals a landscape of interdigitated cis-regulatory archipelagos.

Biological differences between cell types and developmental processes are characterised by differences in gene expression profiles. Gene-distal enhancers are key components of the regulatory networks that specify the tissue-specific expression patterns driving embryonic development and cell fate decisions, and variations in their sequences are a major contributor to genetic disease and disease susceptibility. Despite advances in the methods for discovery of putative cis-regulatory sequences, characterisation of their spatio-temporal enhancer activities in a mammalian model system remains a major bottle-neck.

Defining the relationship between fetal Doppler indices, abdominal circumference and growth rate in severe fetal growth restriction using functional linear discriminant analysis.

The relationship between Doppler measurements, size and growth rate in fetal growth restriction has not been defined. We used functional linear discriminant analysis (FLDA) to investigate these parameters taking account of the difficulties inherent in exploring relationships between repeated observations from a small number of cases. In 40 fetuses with severe growth restriction, serial abdominal circumference (AC), umbilical, middle cerebral artery (MCA) and ductus venosus Doppler pulsatility index measurements were recorded.

Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences.

Pax6 is a developmental control gene essential for eye development throughout the animal kingdom. In addition, Pax6 plays key roles in other parts of the CNS, olfactory system, and pancreas. In mammals a single Pax6 gene encoding multiple isoforms delivers these pleiotropic functions.

Functional characterization of the human RPGR proximal promoter.

Purpose: Mutations in the retinitis pigmentosa (RP) GTPase regulator (RPGR) gene account for more than 70% of X-linked RP cases. This study aims to characterize the proximal promoter region of the human RPGR gene.

Methods: The 5'-flanking region (5 kb) of human RPGR was cloned and sequenced.

Ethanol suppresses phagosomal adhesion maturation, Rac activation, and subsequent actin polymerization during FcγR-mediated phagocytosis.

Clinical and laboratory investigations have provided evidence that ethanol suppresses normal lung immunity. Our initial studies revealed that acute ethanol exposure results in transient suppression of phagocytosis of Pseudomonas aeruginosa by macrophages as early as 3 h after initial exposure. Focusing on mechanisms by which ethanol decreases macrophage Fcγ-receptor (FcγR) phagocytosis we targeted the study on the focal adhesion and cytoskeletal elements that are necessary for phagosome progression.

Guidance for withdrawal and withholding of intensive care as part of neonatal end-of-life care.

Introduction: Advances in foetal medicine and neonatology have enabled increased antenatal diagnosis of life-limiting conditions and improved preterm survival, escalating the debate surrounding the ethics of neonatal end-of-life care and withholding or withdrawing intensive care.

Sources Of Data: Literature search of MEDLINE and the Cochrane library databases using the search terms [neonatal palliative care] AND [neonatal AND withdrawal of intensive care and treatment]. Review of consensus statements and guidelines.

Relationship between placental morphology and histological findings in an unselected population near term.

Whilst individual histological features are well described, there are no universally agreed criteria as to what constitutes a clinically significant histological lesion of the placenta in an uncomplicated pregnancy, nor has the presence of such histological findings been systematically related to quantitative morphological characteristics of the placenta (such as placental shape, cord insertion and cord coiling). This study aims to explore this relationship and further to describe the incidence of predefined categories of histological lesions of the placenta in an unselected obstetric population recruited prior to delivery. The study is based upon the placental examination of 1,156 women with singleton pregnancies recruited prospectively in a single unit.

Prolonged chemokine expression and excessive neutrophil infiltration in the lungs of burn-injured mice exposed to ethanol and pulmonary infection.

Pulmonary infections are a major cause of mortality in the critically ill burn patient. Alcohol consumption before burn increases the risk of pulmonary infection. Previously, we have shown an elevated mortality and lung pathology in mice given ethanol before burn and intratracheal infection relative to controls.

Cord coiling, umbilical cord insertion and placental shape in an unselected cohort delivering at term: relationship with common obstetric outcomes.

Background: The position of the placental cord insertion, its shape and cord coiling are thought to be associated with perinatal outcome. This study derives indices describing the relationship of cord insertion to the placental centre, the shape of the placenta and cord coiling in placentas from unselected term pregnancies. Further, we investigate these indices in pregnancies affected by pre-eclampsia (PET), pregnancy induced hypertension (PIH), gestational diabetes mellitus (GDM) and delivery of a small for gestational age (SGA) baby.