'A good decision is the one that feels right for me': Codesign with patients to inform theoretical underpinning of a decision aid website.

INTRODUCTION: Patient decision aids (PtDA) complement shared decision-making with healthcare professionals and improve decision quality. However, PtDA often lack theoretical underpinning. We are codesigning a PtDA to help people with increased genetic cancer risks manage choices. The aim of an innovative workshop described here was to engage with the people who will use the PtDA regarding the theoretical underpinning and logic model outlining our hypothesis of how the PtDA would lead to more informed decision-making. METHODS: Short presentations about psychological and behavioural theories by an expert were interspersed with facilitated, small-group discussions led by patients. Patients were asked what is important to them when they make health decisions, what theoretical constructs are most meaningful and how this should be applied to codesign of a PtDA. An artist created a visual summary. Notes from patient discussions and the artwork were analysed using reflexive thematic analysis. RESULTS: The overarching theme was: It's personal. Contextual factors important for decision-making were varied and changed over time. There was no one 'best fit' theory to target support needs in a PtDA, suggesting an inductive, flexible framework approach to programme theory would be most effective. The PtDA logic model was revised based on patient feedback. CONCLUSION: Meaningful codesign of PtDA including discussions about the theoretical mechanisms through which they support decision-making has the potential to lead to improved patient care through understanding the intricately personal nature of health decisions, and tailoring content and format for holistic care. PATIENT CONTRIBUTION: Patients with lived experience were involved in codesign and coproduction of this workshop and analysis as partners and coauthors. Patient discussions were the primary data source. Facilitators provided a semi-structured guide, but they did not influence the patient discussions or provide clinical advice. The premise of this workshop was to prioritise the importance of patient lived experience: to listen, learn, then reflect together to understand and propose ideas to improve patient care through codesign of a PtDA.

Veterans with Traumatic Brain Injury-related Ocular Injury and Vision Dysfunction: Recommendations for Rehabilitation.

SIGNIFICANCE: We know the prevalence of traumatic brain injury (TBI)-related vision impairment and ocular injury symptoms. Lacking is an understanding of health care utilization to treat these symptoms. Utilization knowledge is important to structuring access to treatment, identifying clinical training needs, and providing evidence of the effectiveness of treatment. PURPOSE: This article reports rehabilitation, glasses/contacts, and imaging/photography/video recommendations made by optometrists and ophthalmologists as part of the Department of Veterans Affairs-mandated Performance of Traumatic Brain Injury Specific Ocular Health and Visual Functioning Examination administered to veterans with TBI at Department of Veterans Affairs polytrauma specialty facilities. METHODS: Using a retrospective design, natural language processing, and descriptive and regression statistics, data were analyzed for 2458 Operation Enduring Freedom/Operation Iraqi Freedom veterans who were administered the mandated examination between 2008 and 2017. RESULTS: Of the 2458 veterans, vision rehabilitation was recommended for 24%, glasses/contacts were recommended for 57%, and further imaging/photography/video testing was recommended for 58%. Using key words in the referral, we determined that 37% of veterans were referred to blind rehabilitation, 16% to occupational therapy, and 3% to low-vision clinics. More than 50% of the referrals could have been treated by blind rehabilitation, occupational therapy, or low-vision clinics. Rehabilitation referrals were significantly associated with younger age, floaters, photosensitivity, double vision, visual field and balance deficits, dizziness, and difficulty reading. In comparison, prescriptions for glasses and contacts were associated with older age, photosensitivity, blurred vision, decreased visual field and night vision, difficulty reading, and dry eye. Imaging/photography/video testing was associated with floaters, photosensitivity, and headache. CONCLUSIONS: Findings delineate service delivery models available to veterans with TBI-related vision impairment. The challenge these data address is the lack of clear paths from diagnosis of TBI to identification of vision dysfunction deficits to specialized vision rehabilitation, and finally to community reintegration and community based-vision rehabilitation.

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis.

BACKGROUND: Timely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness. METHODS AND FINDINGS: Pregnant women included in the analyses were 22+0 to 34+6 weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an individual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016; 1,783 women; mean age 29.7 years; median BMI 24.8 kg/m2; 67.6% White; 11.7% smokers; 51.8% nulliparous; 10.4% with multiple pregnancy; 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018; 2,924 women; mean age 28.2 years; median BMI 25.4 kg/m2; 88.2% White; 21% smokers; 35.2% nulliparous; 3.5% with multiple pregnancy; 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R2 was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R2 of 36% (95% CI: 34% to 38%). Recalibration of the model's intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than "treat all" or "treat none" strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset. CONCLUSIONS: In this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice. TRIAL REGISTRATION: The study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry (ISRCTN 41598423) and NIHR Portfolio (CPMS: 31277).

Promises and challenges of adoptive T-cell therapies for solid tumours.

Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas-cancer genomics, cancer immunology and cell-therapy manufacturing-that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours.

Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study.

BACKGROUND: Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES). METHODS: In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly. FINDINGS: The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4-11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three [3·2%] of 93 fetuses). INTERPRETATION: WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness. FUNDING: UK Department of Health and Social Care and The Wellcome Trust.

Quantum cascade laser-based reflectance spectroscopy: a robust approach for the classification of plastic type.

The identification of plastic type is important for environmental applications ranging from recycling to understanding the fate of plastics in marine, atmospheric, and terrestrial environments. Infrared reflectance spectroscopy is a powerful approach for plastics identification, requiring only optical access to a sample. The use of visible and near-infrared wavelengths for plastics identification are limiting as dark colored plastics absorb at these wavelengths, producing no reflectance spectra. The use of mid-infrared wavelengths instead enables dark plastics to be identified. Here we demonstrate the capability to utilize a pulsed, widely-tunable (5.59 - 7.41 µm) mid-infrared quantum cascade laser, as the source for reflectance spectroscopy, for the rapid and robust identification of plastics. Through the application of linear discriminant analysis to the resulting spectral data set, we demonstrate that we can correctly classify five plastic types: polyethylene terephthalate (PET), high density polyethylene (HDPE), low density polyethylene (LDPE), polypropylene (PP), and polystyrene (PS), with a 97% accuracy rate.

Rapid Identification of Marine Plastic Debris via Spectroscopic Techniques and Machine Learning Classifiers.

To advance our understanding of the environmental fate and transport of macro- and micro-plastic debris, robust and reproducible methods, technologies, and analytical approaches are necessary for in situ plastic-type identification and characterization. This investigation compares four spectroscopic techniques: attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), near-infrared (NIR) reflectance spectroscopy, laser-induced breakdown spectroscopy (LIBS), and X-ray fluorescence (XRF) spectroscopy, coupled to seven classification methods, including machine learning classifiers, to determine accuracy for identifying type of both consumer plastics and marine plastic debris (MPD). With machine learning classifiers, consumer plastic types were identified with 99, 91, 97, and 70% success rates for ATR-FTIR, NIR reflectance spectroscopy, LIBS, and XRF, respectively. The classification of MPD had similar or lower success rates, likely arising from alterations to the plastic from environmental weathering processes with success rates of 99, 81, 76, and 66% for ATR-FTIR, NIR reflectance spectroscopy, LIBS, and XRF, respectively. Success rates indicate that ATR-FTIR, NIR reflectance spectroscopy, and LIBS coupled with machine learning classifiers can be used to identify both consumer and environmental plastic samples.

Appetite is correlated with octopamine and hemolymph sugar levels in forager honeybees.

Insects have rapidly changing energy demands, so they primarily rely on hemolymph and other carbohydrates to carry out life activities. However, how gustatory responsiveness and hemolymph sugar levels coordinate with one another to maintain energetic homeostasis in insects remains largely unknown for the highly social honeybee that goes through large physiological and behavioral changes. The potential role of biogenic amines and neuropeptides in the connection between the regulation of appetite and fluctuating sugar levels in the hemolymph, due to starvation, as the bee ages, was investigated. The largest appetite increase due to the starvation treatment was within the forager age class and this corresponded with an increase in octopamine levels in the brain along with a decline in hemolymph sugar levels. Adipokinetic hormone (AKH) was found in very small quantities in the brain and there were no significant changes in response to starvation treatment. Our findings suggest that the particularly dynamic levels of hemolymph sugar levels may serve as a monitor of the forager honeybee energetic state. Therefore, there may be a pathway in forager bees via octopamine responsible for their precise precipitous regulation of appetite, but to determine cause and effect relationships further investigation is needed.

Consensus on BCR-ABL1 reporting in chronic myeloid leukaemia in the UK.

For patients with chronic myeloid leukaemia (CML), treatment guidelines recommend monitoring response to treatment with tyrosine kinase inhibitors (TKIs) by testing the BCR-ABL1 fusion gene transcript level using reverse transcriptase quantitative polymerase chain reaction. Despite recent efforts to standardise protocols for BCR-ABL1 testing, some variability remains among laboratories in the UK regarding the techniques used and the approach to reporting results. This increases the risk of misinterpretation of results by both clinicians and patients. An expert panel met to discuss current issues surrounding BCR-ABL1 testing in the UK and to develop guidance for laboratories, with emphasis on the optimal approach to reporting laboratory results. Topics included the minimum required information to include in the laboratory report, units of measurement, test sensitivity and BCR-ABL1 transcript variants. To aid communication between laboratories and clinics, standard forms were generated that could be used by (i) clinics when submitting samples to laboratories, and (ii) laboratories when reporting results to clinics. Standardising the way in which BCR-ABL1 test results are reported from laboratories to clinics should help to improve communication, interpretation of results and patient care.

Partial Photochemical Oxidation Was a Dominant Fate of Deepwater Horizon Surface Oil.

Following the Deepwater Horizon (DWH) blowout in 2010, oil floated on the Gulf of Mexico for over 100 days. In the aftermath of the blowout, substantial accumulation of partially oxidized surface oil was reported, but the pathways that formed these oxidized residues are poorly constrained. Here we provide five quantitative lines of evidence demonstrating that oxidation by sunlight largely accounts for the partially oxidized surface oil. First, residence time on the sunlit sea surface, where photochemical reactions occur, was the strongest predictor of partial oxidation. Second, two-thirds of the partial oxidation from 2010 to 2016 occurred in less than 10 days on the sunlit sea surface, prior to coastal deposition. Third, multiple diagnostic biodegradation indices, including octadecane to phytane, suggest that partial oxidation of oil on the sunlit sea surface was largely driven by an abiotic process. Fourth, in the laboratory, the dominant photochemical oxidation pathway of DWH oil was partial oxidation to oxygenated residues rather than complete oxidation to CO2. Fifth, estimates of partial photo-oxidation calculated with photochemical rate modeling overlap with observed oxidation. We suggest that photo-oxidation of surface oil has fundamental implications for the response approach, damage assessment, and ecosystem restoration in the aftermath of an oil spill, and that oil fate models for the DWH spill should be modified to accurately reflect the role of sunlight.

Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis.

The aim of this study was to characterise adherence in an adult population with cystic fibrosis (CF) and to investigate if variation in lung function was a predictor of adherence to treatment.The adherence of patients aged ≥16 years from an adult CF centre was measured by medication possession ratio (MPR) and self-report. Patients were assigned to one of three adherence categories (<50%, 50 to <80%, ≥80%) by their composite score (MPR). Ordinal regression was used to identify predictors of adherence, including coefficient variation measures for forced expiratory volume in 1 s (FEV1), weight and C-reactive protein concentration, measured from 6 months and 12 months before baseline.MPR data for 106 of 249 patients (mean age 29.8±9.2 years) was retrieved, indicating a mean adherence of 63%. The coefficient of variation for FEV1 was inversely related to adherence and was a univariate predictor of adherence (6 months: OR 0.92, 95% CI 0.87-0.98, p=0.005; 12 months: OR 0.94, 95% CI 0.93-0.99, p=0.03) and remained significant in the final models. The coefficient of variation of weight and C-reactive protein were not predictive of adherence.The coefficient of variation of FEV1 was identified as an objective predictor of adherence. Further evaluation of this potential marker of adherence is now required.

RT-qPCR and RT-Digital PCR: A Comparison of Different Platforms for the Evaluation of Residual Disease in Chronic Myeloid Leukemia.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are the cornerstone of successful clinical management of patients with chronic myeloid leukemia (CML). Quantitative monitoring of the percentage of the fusion transcript BCR-ABL1 (breakpoint cluster region-c-abl oncogene 1, non-receptor tyrosine kinase) BCR-ABL1IS (%BCR-ABL1IS) by reverse transcription-quantitative PCR (RT-qPCR) is the gold standard strategy for evaluating patient response to TKIs and classification into prognostic subgroups. However, this approach can be challenging to perform in a reproducible manner. Reverse-transcription digital PCR (RT-dPCR) is an adaptation of this method that could provide the robust and standardized workflow needed for truly standardized patient stratification. METHODS: BCR-ABL1 and ABL1 transcript copy numbers were quantified in a total of 102 samples; 70 CML patients undergoing TKI therapy and 32 non-CML individuals. 3 commercially available digital PCR platforms (QS3D, QX200 and Raindrop) were compared with the platform routinely used in the clinic for RT-qPCR using the EAC (Europe Against Cancer) assay. RESULTS: Measurements on all instruments correlated well when the %BCR-ABL1IS was ≥0.1%. In patients with residual disease below this level, greater variations were measured both within and between instruments limiting comparable performance to a 4 log dynamic range. CONCLUSIONS: RT-dPCR was able to quantify low-level BCR-ABL1 transcript copies but was unable to improve sensitivity below the level of detection achieved by RT-qPCR. However, RT-dPCR was able to perform these sensitive measurements without use of a calibration curve. Adaptions to the protocol to increase the amount of RNA measured are likely to be necessary to improve the analytical sensitivity of BCR-ABL testing on a dPCR platform.

Novel essential amino acid supplements enriched with L-leucine facilitate increased protein and energy intakes in older women: a randomised controlled trial.

BACKGROUND: Inadequate protein intake (PI), containing a sub-optimal source of essential amino acids (EAAs), and reduced appetite are contributing factors to age-related sarcopenia. The satiating effects of dietary protein per se may negatively affect energy intake (EI), thus there is a need to explore alternative strategies to facilitate PI without compromising appetite and subsequent EI. METHODS: Older women completed two experiments (EXP1 and EXP2) where they consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7.5 g, 40% L-leucine), or nothing (Control). In EXP1, participants (n = 10, 68 ± 5 years, mean ± SD) consumed Bar, Gel or Control with appetite sensations and appetite-related hormonal responses monitored for one hour, followed by consumption of an ad libitum breakfast (ALB). In EXP2, participants (n = 11, 69 ± 5 years) ingested Bar, Gel or Control alongside an ALB. RESULTS: In EXP1, EI at ALB was not different (P = 0.674) between conditions (1179 ± 566, 1254 ± 511, 1206 ± 550 kJ for the Control, Bar, and Gel respectively). However, total EI was significantly higher in the Bar and Gel compared to the Control after accounting for the energy content of the supplements (P < 0.0005). Analysis revealed significantly higher appetite Area under the Curve (AUC) (P < 0.007), a tendency for higher acylated ghrelin AUC (P = 0.087), and significantly lower pancreatic polypeptide AUC (P = 0.02) in the Control compared with the Bar and Gel. In EXP2, EI at ALB was significantly higher (P = 0.028) in the Control (1282 ± 513 kJ) compared to the Bar (1026 ± 565 kJ) and Gel (1064 ± 495 kJ). However, total EI was significantly higher in the Bar and Gel after accounting for the energy content of the supplements (P < 0.007). CONCLUSIONS: Supplementation with either the Bar or Gel increased total energy intake whether consumed one hour before or during breakfast. This may represent an effective nutritional means for addressing protein and total energy deficiencies in older women. TRIAL REGISTRATION: Clinical trial register: retrospectively registered, ISRCTN12977929 on.

Bacteriophage SPP1 tail tube protein self-assembles into ß-structure-rich tubes.

The majority of known bacteriophages have long tails that serve for bacterial target recognition and viral DNA delivery into the host. These structures form a tube from the viral capsid to the bacterial cell. The tube is formed primarily by a helical array of tail tube protein (TTP) subunits. In phages with a contractile tail, the TTP tube is surrounded by a sheath structure. Here, we report the first evidence that a phage TTP, gp17.1 of siphophage SPP1, self-assembles into long tubes in the absence of other viral proteins. gp17.1 does not exhibit a stable globular structure when monomeric in solution, even if it was confidently predicted to adopt the ß-sandwich fold of phage λ TTP. However, Fourier transform infrared and nuclear magnetic resonance spectroscopy analyses showed that its ß-sheet content increases significantly during tube assembly, suggesting that gp17.1 acquires a stable ß-sandwich fold only after self-assembly. EM analyses revealed that the tube is formed by hexameric rings stacked helicoidally with the same organization and helical parameters found for the tail of SPP1 virions. These parameters were used to build a pseudo-atomic model of the TTP tube. The large loop spanning residues 40-56 is located on the inner surface of the tube, at the interface between adjacent monomers and hexamers. In line with our structural predictions, deletion of this loop hinders gp17.1 tube assembly in vitro and interferes with SPP1 tail assembly during phage particle morphogenesis in bacteria.

Evaluating a Midwife-Led Model of Antenatal Care for Women with a Previous Cesarean Section: A Retrospective, Comparative Cohort Study.

BACKGROUND: Research is yet to identify effective and safe interventions to increase the vaginal birth after cesarean (VBAC) rate. This research aimed to compare intended and actual VBAC rates before and after implementation of midwife-led antenatal care for women with one previous cesarean birth and no other risk factors in a large, tertiary maternity hospital in England. METHODS: This was a retrospective, comparative cohort study. Data were collected from the medical records of women with one previous lower segment cesarean delivery and no other obstetric, medical, or psychological complications who gave birth at the hospital before (2008) and after (2011) the implementation of midwife-led antenatal care. Chi-squared analysis was used to calculate the odds ratio, and logistic regression to account for confounders. RESULTS: Intended and actual VBAC rates were higher in 2011 compared with 2008: 90 percent vs. 77 percent, adjusted odds ratio (aOR) 2.69 (1.48-4.87); and 61 percent vs. 47 percent, aOR 1.79 (1.17-2.75), respectively. Mean rates of unscheduled antenatal care sought via the delivery suite and inpatient admissions were lower in 2011 than 2008. Postnatal maternal and neonatal safety outcomes were similar between the two groups, except mean postnatal length of stay, which was shorter in 2011 compared with 2008 (2.67 vs. 3.15 days). CONCLUSIONS: Implementation of midwife-led antenatal care for women with one previous cesarean offers a safe and effective alternative to traditional obstetrician-led antenatal care, and is associated with increased rates of intended and actual VBAC.

Clinical science workshop: targeting the gut-liver-brain axis.

A clinical science workshop was held at the ISHEN meeting in London on Friday 11th September 2014 with the aim of thrashing out how we might translate what we know about the central role of the gut-liver-brain axis into targets which we can use in the treatment of hepatic encephalopathy (HE). This review summarises the integral role that inter-organ ammonia metabolism plays in the pathogenesis of HE with specific discussion of the roles that the small and large intestine, liver, brain, kidney and muscle assume in ammonia and glutamine metabolism. Most recently, the salivary and gut microbiome have been shown to underpin the pathophysiological changes which culminate in HE and patients with advanced cirrhosis present with enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across a leaky gut epithelial barrier. Resident macrophages within the liver are able to sense bacterial degradation products initiating a pro-inflammatory response within the hepatic parenchyma and release of cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-8 into the systemic circulation. The endotoxemia and systemic inflammatory response that are generated predispose both to the development of infection as well as the manifestation of covert and overt HE. Co-morbidities such as diabetes and insulin resistance, which commonly accompany cirrhosis, may promote slow gut transit, promote bacterial overgrowth and increase glutaminase activity and may need to be acknowledged in HE risk stratification assessments and therapeutic regimens. Therapies are discussed which target ammonia production, utilisation or excretion at an individual organ level, or which reduce systemic inflammation and endotoxemia which are known to exacerbate the cerebral effects of ammonia in HE. The ideal therapeutic strategy would be to use an agent that can reduce hyperammonemia and reduce systemic inflammation or perhaps to adopt a combination of therapies that can address both.

Impact of the Deepwater Horizon oil spill on a deep-water coral community in the Gulf of Mexico.

To assess the potential impact of the Deepwater Horizon oil spill on offshore ecosystems, 11 sites hosting deep-water coral communities were examined 3 to 4 mo after the well was capped. Healthy coral communities were observed at all sites >20 km from the Macondo well, including seven sites previously visited in September 2009, where the corals and communities appeared unchanged. However, at one site 11 km southwest of the Macondo well, coral colonies presented widespread signs of stress, including varying degrees of tissue loss, sclerite enlargement, excess mucous production, bleached commensal ophiuroids, and covering by brown flocculent material (floc). On the basis of these criteria the level of impact to individual colonies was ranked from 0 (least impact) to 4 (greatest impact). Of the 43 corals imaged at that site, 46% exhibited evidence of impact on more than half of the colony, whereas nearly a quarter of all of the corals showed impact to >90% of the colony. Additionally, 53% of these corals' ophiuroid associates displayed abnormal color and/or attachment posture. Analysis of hopanoid petroleum biomarkers isolated from the floc provides strong evidence that this material contained oil from the Macondo well. The presence of recently damaged and deceased corals beneath the path of a previously documented plume emanating from the Macondo well provides compelling evidence that the oil impacted deep-water ecosystems. Our findings underscore the unprecedented nature of the spill in terms of its magnitude, release at depth, and impact to deep-water ecosystems.

A comparison of bolus track and test bolus computed tomography pulmonary angiography and the implications on pulmonary and aortic vessel enhancement, effective dose and suboptimal scan rate.

INTRODUCTION: Bolus track and test bolus are the most commonly used contrast timing protocols to undertake computed tomography pulmonary angiography (CTPA). The aim of this study was to compare test bolus and bolus track contrast enhancement protocols in terms of enhancement of the pulmonary vessels and aorta, radiation dose and suboptimal scan rate to determine the optimal technique for CTPA. METHODS: A total of 200 CTPA examinations (100 using each protocol) performed between January and February 2021 were assessed retrospectively. All scans were performed on a 2x128 Dual Source Siemens Drive Scanner. CT attenuation was measured in Hounsfield Units (HU), with measurements taken from the main pulmonary trunk, right pulmonary artery and left pulmonary artery, ascending and descending aorta. The mean effective dose was calculated from the dose-length product (DLP). The suboptimal scan rate was calculated as the percentage of examinations below 210HU. RESULTS: The average HU of the pulmonary arteries was 358 HU ± SD 129.2 in the test bolus group and increased to 394 HU ± SD 133.9 in the bolus track group with a P value of ≤0.05. The average HU of the aorta was 235 HU ± SD 82.8 in the test bolus group and increased to 319 HU ± SD 91.8 in the bolus track group with a P value of <0.001. Although not statistically significant, the mean effective dose was reduced by 4.2% for the bolus track protocol (2.4 mSv vs. 2.5 mSv, P > 0.05). Fewer suboptimal scans were performed with the bolus track protocol (5 scans <210HU Bolus Track vs. 9 scans <210HU Test Bolus). CONCLUSION: The bolus track protocol results in increased enhancement of the pulmonary arteries and aorta, with the added benefits of a lower suboptimal scan rate and lower effective dose.

Chilean midwives' experiences while providing induced abortion care after the enactment of a law decriminalising abortion.

INTRODUCTION: The recent change in Chilean legislation towards abortion enabled midwives to include the care of women having an induced abortion within their scope of practice. However, midwives' identity could be strained by induced abortion care provision as it is contrary to midwives' traditional role. Considering this, the aim of the study was to elucidate how Chilean midwives understand and provide abortion care. METHODS: A constructivist grounded theory study was conducted using online semi-structured in-depth interviews. Midwives were purposively sampled considering maximum variation criteria and then theoretical sampling occurred. Saturation was achieved with fifteen interviews. Interviews were conducted in Spanish and then translated into English. Constant comparison analysis generated categories. Data were managed using NVivo 12. All interviewees provided their consent to be part of this study. RESULTS: This article reports on the experiences of nine midwives who had provided lawful induced abortion care in Chile. The experiences of these midwives were grouped into two major categories: 'Defining a position towards abortion' and 'Abortion care is emotional labour'. CONCLUSION: Midwives can successfully provide abortion care despite being challenged by certain areas of it. Considering the high demand for emotional labour in abortion care, efforts should be made to increase midwives' emotional self-regulation skills. Likewise, organisations should strengthen and implement their offer of well-being and emotional self-care support to midwives.

Navigating a maze: Midwives' identity response to the enactment of an abortion law in Chile.

BACKGROUND: Chilean midwives have been identified as essential for successfully implementing an abortion law, a practice which could potentially be understood as contradicting their central mission. Nevertheless, to date, there has been no investigation into how Chilean midwives have incorporated induced abortion care provision into their professional identity. OBJECTIVE: To elucidate how Chilean midwives understand and provide abortion care and how they have (re)defined their professional identity to include induced abortion care. This article reports the findings of the second part of this aim. METHODS: This study was underpinned by a constructivist grounded theory methodology informed by a reproductive justice and feminist perspective. Midwives from Chile who have cared for women undergoing abortion were invited to participate in the study. After purposive and theoretical sampling, fifteen midwives were recruited. FINDINGS: Midwives' identity is woman-centred, with high value placed on their role protecting life. These two aspects of midwives' identity are in contradiction when providing abortion care. Midwives' identity results from and informs midwives' practice. Midwifery regulation influences both practice and identity. The model 'Navigating a maze' explains the interaction of these three elements. CONCLUSION: Midwives' identity response to the enactment of the Chilean abortion law is an example of how professional identity must navigate regulation and practice to make sense of its purpose. In light of this study's findings, the current tension experienced in midwives' identity should be carefully attended to prevent adverse outcomes for midwives and the Chilean population.