Differences in Cardiometabolic Proteins in Pregnancy Prioritize Relevant Targets of Preeclampsia.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet need for the prevention of adverse pregnancy outcomes. METHODS: We explored differences in cardiovascular proteomics (Olink Explore 384) in 256 diverse pregnant persons across 2 centers (26% Hispanic, 21% Black). RESULTS: We identified significant differences in plasma abundance of markers associated with angiogenesis, blood pressure, cell adhesion, inflammation, and metabolism between individuals delivering with preeclampsia and controls, some of which have not been widely described previously and are not represented in the preeclampsia placental transcriptome. While we observed a broadly similar pattern in early (<34 weeks) versus late (≥34 weeks) preeclampsia, several proteins related to hemodynamic stress, hemostasis, and immune response appeared to be more highly dysregulated in early preeclampsia relative to late preeclampsia. CONCLUSIONS: These results demonstrate the value of performing targeted proteomics using a panel of cardiovascular biomarkers to identify biomarkers relevant to preeclampsia pathophysiology and highlight the need for larger multiomic studies to define modifiable pathways of surveillance and intervention upstream to preeclampsia diagnosis.

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies. METHODS: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. RESULTS: Recruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e' (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001). CONCLUSIONS: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

Elevation of Postmortem Cerebrospinal Fluid Sodium and Chloride Levels Is a Potential Adjunct Test in the Diagnosis of Salt Water Drowning.

Postmortem vitreous humor biochemistry is a useful test in the diagnosis of salt water drowning (SWD). A significant limitation of vitreous humor is the potential effect of prolonged immersion. A recent animal study and case report suggested that cerebrospinal fluid biochemistry may be an alternative to vitreous because it is more resistant to the effects of immersion, given its protected anatomical location. This study compared postmortem cerebrospinal fluid sodium and chloride (PMCSC) levels collected via ventricular aspiration (PMCSC_V) and via lumbar puncture (PMCSC_L) in 13 SWD and 31 nonimmersion deaths. It showed a significant elevation in PMCSC levels in SWD deaths for both PMCSC_V and PMCSC_L (P < 0.05). The areas under the curve on the receiver operating characteristic curves for PMCSC_V and PMCSC_L were 0.73 and 0.83, respectively. The optimal cutoff for PMCSC_V was 216 mmol/L (sensitivity, 0.60; specificity, 0.72; likelihood ratio, 1.80; positive predictive value, 0.45) and for PMCSC_L was 241 mmol/L (sensitivity, 0.78; specificity, 0.73; likelihood ratio, 2.89; positive predictive value, 0.46). This study supports PMCSC levels as another biochemical test that can potentially aid in the diagnosis of SWD, particularly in cases where vitreous humor samples are unavailable or uninterpretable.

Googling endometriosis: a systematic review of information available on the Internet.

BACKGROUND: The demand for health information online is increasing rapidly without clear governance. OBJECTIVE: We aim to evaluate the credibility, quality, readability, and accuracy of online patient information concerning endometriosis. STUDY DESIGN: We searched 5 popular Internet search engines: aol.com, ask.com, bing.com, google.com, and yahoo.com. We developed a search strategy in consultation with patients with endometriosis, to identify relevant World Wide Web pages. Pages containing information related to endometriosis for women with endometriosis or the public were eligible. Two independent authors screened the search results. World Wide Web pages were evaluated using validated instruments across 3 of the 4 following domains: (1) credibility (White Paper instrument; range 0-10); (2) quality (DISCERN instrument; range 0-85); and (3) readability (Flesch-Kincaid instrument; range 0-100); and (4) accuracy (assessed by a prioritized criteria developed in consultation with health care professionals, researchers, and women with endometriosis based on the European Society of Human Reproduction and Embryology guidelines [range 0-30]). We summarized these data in diagrams, tables, and narratively. RESULTS: We identified 750 World Wide Web pages, of which 54 were included. Over a third of Web pages did not attribute authorship and almost half the included pages did not report the sources of information or academic references. No World Wide Web page provided information assessed as being written in plain English. A minority of web pages were assessed as high quality. A single World Wide Web page provided accurate information: evidentlycochrane.net. Available information was, in general, skewed toward the diagnosis of endometriosis. There were 16 credible World Wide Web pages, however the content limitations were infrequently discussed. No World Wide Web page scored highly across all 4 domains. CONCLUSION: In the unlikely event that a World Wide Web page reports high-quality, accurate, and credible health information it is typically challenging for a lay audience to comprehend. Health care professionals, and the wider community, should inform women with endometriosis of the risk of outdated, inaccurate, or even dangerous information online. The implementation of an information standard will incentivize providers of online information to establish and adhere to codes of conduct.

Studies of a Large Odd-Numbered Odd-Electron Metal Ring: Inelastic Neutron Scattering and Muon Spin Relaxation Spectroscopy of Cr8 Mn.

The spin dynamics of Cr8 Mn, a nine-membered antiferromagnetic (AF) molecular nanomagnet, are investigated. Cr8 Mn is a rare example of a large odd-membered AF ring, and has an odd-number of 3d-electrons present. Odd-membered AF rings are unusual and of interest due to the presence of competing exchange interactions that result in frustrated-spin ground states. The chemical synthesis and structures of two Cr8 Mn variants that differ only in their crystal packing are reported. Evidence of spin frustration is investigated by inelastic neutron scattering (INS) and muon spin relaxation spectroscopy (µSR). From INS studies we accurately determine an appropriate microscopic spin Hamiltonian and we show that µSR is sensitive to the ground-spin-state crossing from S=1/2 to S=3/2 in Cr8 Mn. The estimated width of the muon asymmetry resonance is consistent with the presence of an avoided crossing. The investigation of the internal spin structure of the ground state, through the analysis of spin-pair correlations and scalar-spin chirality, shows a non-collinear spin structure that fluctuates between non-planar states of opposite chiralities.

Paediatric aeromedical retrievals in the 'Top End' of the Northern Territory.

OBJECTIVE: The primary objective of this study was to describe the remote paediatric aeromedical population of the 'Top End' of the Northern Territory. The secondary objective was to identify children requiring high-dependency care by the transport team. DESIGN: Retrospective case review. SETTING: Aeromedical service in the remote Northern Territory. PARTICIPANTS: All patients under the age of 16 years transported over a one-year period between February 2012 and February 2013. OUTCOME MEASURES: Age, gestation if newborn, diagnosis at referral, requirement for high-dependency care and transport team members. RESULTS: Seven hundred eighty-nine children were transported with an average age of 4.4 years (range 0 days to 16 years). Nursing staff transferred 646 (82%). Respiratory problems (bronchiolitis and pneumonia) were the predominant illness type (31%). Other frequent diagnoses were trauma (11%), gastroenteritis (10%), cellulitis or abscess (9%) and the sequelae of streptococcal infection (8%). Thirty preterm infants including seven below 31 weeks gestation were transferred. Twenty-five children required high-dependency care, 15 of these on day 0 of life. Twenty-five required respiratory support, seven central venous access, four surfactant, two inotropes and one chest tubes. CONCLUSIONS: The majority of paediatric aeromedical patients have an infective cause for their illness. Respiratory disease is the most common indication for aeromedical transport. The majority of patients are transferred by a flight nurse and do not require high-dependency care. The main risk factor identified for requiring high-dependency care during transport is respiratory distress in a newborn infant.

Assessment of heart-substructures auto-contouring accuracy for application in heart-sparing radiotherapy for lung cancer.

Objectives: We validated an auto-contouring algorithm for heart substructures in lung cancer patients, aiming to establish its accuracy and reliability for radiotherapy (RT) planning. We focus on contouring an amalgamated set of subregions in the base of the heart considered to be a new organ at risk, the cardiac avoidance area (CAA), to enable maximum dose limit implementation in lung RT planning. Methods: The study validates a deep-learning model specifically adapted for auto-contouring the CAA (which includes the right atrium, aortic valve root, and proximal segments of the left and right coronary arteries). Geometric, dosimetric, quantitative, and qualitative validation measures are reported. Comparison with manual contours, including assessment of interobserver variability, and robustness testing over 198 cases are also conducted. Results: Geometric validation shows that auto-contouring performance lies within the expected range of manual observer variability despite being slightly poorer than the average of manual observers (mean surface distance for CAA of 1.6 vs 1.2 mm, dice similarity coefficient of 0.86 vs 0.88). Dosimetric validation demonstrates consistency between plans optimized using auto-contours and manual contours. Robustness testing confirms acceptable contours in all cases, with 80% rated as "Good" and the remaining 20% as "Useful." Conclusions: The auto-contouring algorithm for heart substructures in lung cancer patients demonstrates acceptable and comparable performance to human observers. Advances in knowledge: Accurate and reliable auto-contouring results for the CAA facilitate the implementation of a maximum dose limit to this region in lung RT planning, which has now been introduced in the routine setting at our institution.

Radiotherapy intensification for atypical and malignant meningiomas: A systematic review.

Background: The outcomes of nonbenign (WHO Grades 2 and 3 [G2, G3]) meningiomas are suboptimal and radiotherapy (RT) dose intensification strategies have been investigated. The purpose of this review is to report on clinical practice and outcomes with particular attention to RT doses and techniques. Methods: The PICO criteria (Population, Intervention, Comparison, and Outcomes) were used to frame the research question, directed at outlining the clinical outcomes in patients with G2-3 meningiomas treated with RT. The same search strategy was run in Embase and MEDLINE and, after deduplication, returned 1 807 records. These were manually screened for relevance and 25 were included. Results: Tumor outcomes and toxicities are not uniformly reported in the selected studies since different endpoints and time points have been used by different authors. Many risk factors for worse outcomes are described, the most common being suboptimal RT. This includes no or delayed RT, low doses, and older techniques. A positive association between RT dose and progression-free survival (PFS) has been highlighted by analyzing the studies in this review (10/25) that report the same endpoint (5y-PFS). Conclusions: This literature review has shown that standard practice RT leads to suboptimal tumor control rates in G2-3 meningiomas, with a significant proportion of disease recurring after a relatively short follow-up. Randomized controlled trials are needed in this setting to define the optimal RT approach. Given the increasing data to suggest a benefit of higher RT doses for high-risk meningiomas, novel RT technologies with highly conformal dose distributions are preferential to achieve optimal target coverage and organs at risk sparing.

Obstetric air medical retrievals in the Australian outback.

INTRODUCTION: Women in labor or with complications of pregnancy in the remote, outback region of Australia's Northern Territory are transported to the hospital by air. The objective of this study was to describe the interventions required by obstetric and newborn patients during air medical transport and to evaluate how often these were beyond the scope of practice of a team consisting of an experienced midwife with or without a general flight doctor. METHODS: A retrospective cohort analysis of 200 consecutive women between 20 weeks gestation up to 24 hours postpartum and newborns transferred during the same time period. RESULTS: Only 1 obstetric patient required intervention beyond the scope of a midwife. Forty-eight newborn infants were transferred. Eleven (23%) required interventions within the skill range of a general flight doctor. Twenty (42%) required neonatal specialist care. Ten of 31 newborns requiring more than midwifery care were referred for transport while in utero. CONCLUSIONS: In this specific cohort, a midwife provided an appropriate level of maternal care to the majority of patients. Newborns frequently required clinical expertise beyond the practice scope of a midwife and general flight doctor. Most women in labor do not deliver during transport. The transport service has finite economic resources and logistical constraints. This study highlighted an ongoing challenge regarding when to request additional neonatal specialist care for preterm or high-risk patients referred for transport in utero.

The truth project paper one-how did victims and survivors experience participation? Addressing epistemic relational inequality in the field of child sexual abuse.

The last 30 years has seen an exponential increase in Historical Institutional Abuse Inquiries. One feature of these has been to place adult survivor voices at the center of Inquiry work, meaning that child abuse victims and survivors are engaging with Inquiries, sharing their experiences, with this participation often presented as empowering and healing. This initiative challenges long held beliefs that child sexual abuse survivors are unreliable witnesses, which has led to epistemic injustice and a hermeneutical lacunae in survivor testimony. However to date there has been limited research on what survivors say about their experiences of participation. The Truth Project was one area of work of the Independent Inquiry into Child Sexual Abuse in England and Wales. It invited survivors of Child Sexual Abuse to share their experiences including the impacts of abuse and their recommendations for change. The Truth Project concluded in 2021 and heard from more than 6,000 victims of child sexual abuse. The evaluation of the Trauma Informed Approach designed to support survivors through their engagement with the project was a mixed methods, two phase methodology. A total of 66 survey responses were received. Follow-up interviews were conducted with seven survey respondents. The Trauma Informed Approach was found to be predominantly helpful in attending to victim needs and minimizing harm. However, a small number of participants reported harmful effects post-session. The positive impacts reported about taking part in the Truth Project as a one-off engagement challenges beliefs that survivors of child sexual abuse cannot safely talk about their experiences. It also provides evidence of the central role survivors should have in designing services for trauma victims. This study contributes to the epistemic justice literature which emphasizes the central role of relational ethics in the politics of knowing, and the importance of developing a testimonial sensibility when listening to marginalized groups.

The truth project- paper two- using staff training and consultation to inculcate a testimonial sensibility in non-specialist staff teams working with survivors of child sexual abuse.

This paper explores how trauma informed training and consultation for non-specialist staff at the Independent Inquiry into Child Sexual Abuse in England and Wales enabled them to work with survivors of non-recent child sexual abuse in the Truth Project and other areas of the Inquiry. The paper draws on data gathered from 32 semi-structured interviews with a range of Inquiry staff, including civil servants, legal professionals, senior operational managers, and researchers. The interview questions mapped on to the trauma informed principles embedded in the Inquiry and considered the efficacy and implementation of this training for engaging with survivors' voices, working with challenging testimonies and materials, and contributing to epistemic change. Findings included all staff having an awareness of what it meant to be trauma informed in an Inquiry context, talking about the principles in terms of value-based positions. Staff described an awareness of needing to attend to the idiosyncratic experiences of the individual survivor, and there was recognition that previous damage to survivor trust, through institutional failure, meant that demonstrating trustworthiness was a central task. Staff talked about the impacts of participation on some survivors, and the impacts it had on them to be exposed to trauma-related materials. There was acknowledgment of the limitations of the trauma informed approach but also recognition of the wider applications of this learning for other areas of their personal and professional lives. There is some support for the therapeutic culture developed at the Inquiry leading to what Fricker refers to as a testimonial sensibility, a quality of listening necessary for the establishment of epistemic justice. The discussion focuses on how this way of working can be applied to other public service settings and how epistemic justice concepts can be included in more traditional trauma informed care models to encourage an ethic of listening that has political and social, in addition to therapeutic, outcomes.

Pediatric Ventricular Assist Device Implantation: An Anesthesia Perspective.

BACKGROUND: Ventricular assist devices (VADs) are increasingly being implanted in children, yet there is little literature to guide anesthetic management for these procedures. AIMS: To describe the pediatric population presenting for VAD implantation and the anesthetic management these patients receive. To compare (a) children under and over 12 months of age and (b) children with and without congenital heart disease. METHODS: Retrospective review of patients aged 0 to 17 years who underwent VAD implantation at a single center between 2014 and 2019. RESULTS: Seventy-seven VADs were implanted in 68 patients (46 left VADs, 24 biventricular VADs, 6 right VADs, and 1 univentricular VAD). One procedure was abandoned. Preoperatively, 20 (26%) patients were supported with extracorporeal membrane oxygenation and 57 (73%) patients were ventilated. Intraoperative donor blood products were required in 74 (95%) cases. Postimplantation inotropic support was required in 66 (85%) cases overall and 46 (100%) patients receiving a left VAD. Infants under 12 months were more likely to require preoperative extracorporeal membrane oxygenation (42% vs 19%), have femoral venous access (54% vs 28%), receive an intraoperative vasoconstrictor (42% vs 24%), and have delayed sternal closure (63 vs 22%). Mortality was higher in patients under 12 months (25% vs 19%) and in patients with congenital heart disease (25% vs 20%). CONCLUSIONS: Children undergoing VAD implantation require high levels of preoperative organ support, high-dose intraoperative inotropic support, and high-volume blood transfusion. Children under 12 months and those with congenital heart disease are particularly challenging for anesthesiologists and have worse overall outcomes.

The Chondrogenic Potential of First-Trimester and Term Placental Mesenchymal Stem/Stromal Cells.

OBJECTIVES: Mesenchymal stem/stromal cells (MSCs) are a well-established cell source for cartilage engineering, but challenges remain as differentiation often results in chondrocyte hypertrophy. Chondrogenic potential also varies with MSC source and donor age. We assessed the chondrogenic potential of first-trimester and term placental MSCs and compared their response to commonly used bone marrow MSCs (BM-MSCs). DESIGN: MSCs were isolated from first-trimester and term placentae. BM-MSCs were commercially obtained. Chondrogenesis was induced by micromass culture in commercial chondrogenic media for 7, 14, or 21 days. Pellets were assessed for glycosaminoglycan (GAG) content, and types I, II, and X collagen. Gene expression was profiled using Qiagen RT2 human MSC arrays. RESULTS: At day 0, first-trimester and term MSCs expression levels of many chondrogenic genes to BM-MSC after 21 days of culture. Only first trimester MSCs showed significant changes in chondrogenic gene expression during induction compared to day 0 undifferentiated MSCs (greater BMP4, KAT2B, and reduced GDF6 expression). Additionally, first-trimester MSCs showed significantly greater expression of ABCB1 (at days 14 and 21) and BMP4 (at days 7, 14, 21) compared with term MSCs. Both first-trimester and term pellets showed increased GAG content over time and term MSCs had significantly GAG greater compared with BM-MSCs at days 7 and 14. Type II collagen was present in all pellets but unlike BM-MSCs, type I collagen was not observed in first-trimester or term MSC pellets. CONCLUSIONS: These data highlight differences in BM-MSC and placental MSC chondrogenesis and demonstrate that placental MSCs may be an alternative cell source.

Googling fibroids: A critical appraisal of information available on the internet.

OBJECTIVE: We aim to evaluate the accuracy, quality, and readability of online patient information concerning fibroids. STUDY DESIGN: We searched the most popular Internet search engine: Google.com. We developed a search strategy in consultation with patients with fibroids, to identify relevant websites. Two independent authors screened the search results. Websites were evaluated using validated instruments across three domains, including assessments of: [1] quality (DISCERN instrument; range 0-85); [2] readability (Flesch-Kincaid instrument; range 0-100); and [3] accuracy. Accuracy was assessed using evidence-based statements. We summarised this data narratively including the use of figures and tables. RESULTS: We identified 750 websites, of which 48 were included. Over a third of websites did not attribute authorship and almost half the included websites did not report the sources of information or academic references. No website provided written patient information in line with recommendations from the American Medical Association. A minority (18%) of websites were assessed as high quality. Twelve webpages provided only accurate statements. Available information was, in general, skewed towards the surgical management of fibroids. No website scored highly across all three domains. CONCLUSION: In the unlikely event that a website reports high quality and accurate health information, it is typically challenging for a lay audience to comprehend. Healthcare professionals and the wider community, should inform women with fibroids of the risk of outdated, inaccurate, or even dangerous information online. The implementation of an Information Standard certification will incentivise providers of online information to establish and adhere to codes of conduct. VIDEO ABSTRACT.

An introduction to proton beam therapy.

Radiotherapy is a highly effective anti-cancer treatment commonly used alongside systemic therapies and surgery to achieve long-term cancer-free survival. Conventional radiotherapy uses photon beams to deliver a high dose of radiation to the tumour volume to eradicate cancer cells. This has to be offset against the irradiation of surrounding normal tissues, as increasing this dose causes more treatment-related toxicity. In August 2018, the NHS's first high energy proton beam therapy centre opened at The Christie NHS Foundation Trust in Manchester. A second NHS centre is scheduled to open in 2020 at the University College London Hospitals NHS Trust. Proton beam therapy may offer dosimetric advantages compared to conventional radiotherapy as a result of its characteristic dose deposition - proton beams deliver a comparatively higher proportion of their dose to the target volume relative to normal tissues, without significant exit doses when compared to conventional photon therapy. Therefore proton beam therapy may be indicated for certain tumours situated next to critical organs or in the paediatric population where quality of life and the reduction of secondary effects from radiation are particularly significant. The indications for proton beam therapy and patient outcomes after treatment will be carefully monitored and evaluated in order to provide a robust evidence base for its use.

Contemporary outcomes from the use of regular imaging to detect relapse in high-risk cutaneous melanoma.

BACKGROUND: Agreement on the utility of imaging follow-up in patients with high-risk melanoma is lacking. A UK consensus statement recommends a surveillance schedule of CT or positron-emission tomography-CT and MRI brain (every 6 months for 3 years, then annually in years 4 and 5) as well as clinical examination for high-risk resected Stages II and III cutaneous melanoma. Our aim was to assess patterns of relapse and whether imaging surveillance could be of clinical benefit. PATIENTS AND METHODS: A retrospective study of patients enrolled between July 2013 and June 2015 from three UK tertiary cancer centres followed-up according to this protocol was undertaken. We evaluated time-to-recurrence (TTR), recurrence-free survival (RFS), method of detection and characteristics of recurrence, treatment received and overall survival (OS). RESULTS: A total of 173 patients were included. Most (79%) had treated Stages IIIB and IIIC disease. With a median follow-up of 23.3 months, 82 patients (47%) had relapsed. Median TTR was 10.1 months and median RFS was 21.2 months. The majority of recurrences (66%) were asymptomatic and detected by scheduled surveillance scan. Fifty-six (68%) patients recurred with Stage IV disease, with a median OS of 25.3 months; 26 (31.7%) patients had a locoregional recurrence, median OS not reached (P=0.016). Patients who underwent surgery at recurrence for either Stage III (27%) or IV (18%) disease did not reach their median OS. The median OS for the 33 patients (40%) who received systemic therapy was 12.9 months. CONCLUSION: Imaging appears to reliably detect subclinical disease and identify patients suitable for surgery, conferring favourable outcomes. The short median TTR provides rationale to intensify imaging schedule in the first year of surveillance. The poor OS of patients treated with systemic therapy probably reflects the relatively inferior treatment options during this time and requires further evaluation in the current era.

Prenatal diagnosis of pulmonary atresia: impact on clinical presentation and early outcome.

AIM: The impact of prenatal diagnosis on morbidity and mortality for certain types of congenital heart disease (obstructive left heart lesions and transposition of the great arteries) is well established. No data are available for lesions with duct dependent pulmonary flow. We aimed to assess the impact of prenatal diagnosis of pulmonary atresia on clinical presentation and neonatal outcome. METHOD: Fifty-eight newborns with pulmonary atresia presenting to our centre were identified retrospectively between 1997 and 2004 (prenatal diagnosis n = 37, postnatal n = 21). Anatomical sub-types included intact ventricular septum (PAIVS, n = 33) and ventricular septal defect (PAVSD, n = 25); those with more complex anatomy were excluded. RESULTS: After adjusting for anatomical sub-type, postnatally diagnosed infants were significantly more hypoxic at presentation (mean oxygen saturation 65% vs 84%). However, they presented early (median age 1 day) and prostaglandin E was initiated promptly (median 3 hours) with rapid improvement of oxygen saturations (interaction p<0.001). This resulted in no appreciable differences in terms of pH, base deficit, blood pressure or heart rate between the groups by the time of the first catheter/surgical intervention. Postnatal infants did not differ in terms of length of intensive care unit (p = 0.18) or hospital stay (p = 0.86), incidence of complications (p = 0.72), or mortality (p = 0.77). Multivariable analysis revealed a positive association between occurrence of complications and both degree of cyanosis at presentation (rather than postnatal diagnosis per se) and anatomy (PAIVS). CONCLUSION: Postnatal diagnosis of pulmonary atresia is associated with greater cyanosis at presentation. However this does not translate into greater neonatal morbidity or mortality provided that early recognition and prompt initiation of prostaglandin E therapy occur.

Protocol for developing, disseminating and implementing a core outcome set for endometriosis.

INTRODUCTION: Endometriosis is a common gynaecological disease characterised by pain and subfertility. Randomised controlled trials evaluating treatments for endometriosis have reported many different outcomes and outcome measures. This variation restricts effective data synthesis limiting the usefulness of research to inform clinical practice. To address these methodological concerns, we aim to develop, disseminate and implement a core outcome set for endometriosis engaging with key stakeholders, including healthcare professionals, researchers and women with endometriosis. METHODS AND ANALYSIS: An international steering group has been established, including healthcare professionals, researchers and patient representatives. Potential outcomes identified from a systematic review of the literature will be entered into a modified Delphi method. Key stakeholders will be invited to participate including healthcare professionals, researchers and women with endometriosis. Participants will be invited to score individual outcomes on a nine-point Likert scale anchored between 1 (not important) and 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group converge towards consensus, 'core', outcomes. High-quality outcome measures will be associated with core outcomes. ETHICS AND DISSEMINATION: The implementation of a core outcome set for endometriosis within future clinical trials, systematic reviews and clinical guidelines will enhance the availability of comparable data to facilitate evidence-based patient care. This study was prospectively registered with Core Outcome Measures in Effectiveness Trials Initiative; number: 691.

Heterodimers of heterometallic rings.

Nine new complexes are reported involving linked heterometallic rings; one ring is designed as a ligand for the second, and the compounds produced can be regarded as molecular prototypes for implementing quantum gates featuring two subtly different qubits.