Resilience to periodic disturbances and the long-term genetic stability in Acropora coral.

Climate change is restructuring natural ecosystems. The direct impacts of these events on biodiversity and community structure are widely documented, but the impacts on the genetic variation of populations remains largely unknown. We monitored populations of Acropora coral on a remote coral reef system in northwest Australia for two decades and through multiple cycles of impact and recovery. We combined these demographic data with a temporal genetic dataset of a common broadcast spawning corymbose Acropora to explore the spatial and temporal patterns of connectivity underlying recovery. Our data show that broad-scale dispersal and post-recruitment survival drive recovery from recurrent disturbances, including mass bleaching and mortality. Consequently, genetic diversity and associated patterns of connectivity are maintained through time in the broader metapopulation. The results highlight an inherent resilience in these globally threatened species of coral and showcase their ability to cope with multiple disturbances, given enough time to recover is permitted.

Paediatric tibial shaft fractures: an instructional review for the FRCS exam.

This instructional review presents the literature and guidelines relevant to the classification, management and prognosis of paediatric tibial shaft fractures at a level appropriate for the FRCS exit examination in Trauma and Orthopaedic surgery.

A comparison of self-reported risk and protective factors and the death implicit association test in the prediction of future suicide attempts in adolescent emergency department patients.

BACKGROUND: Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings. METHODS: A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics. RESULTS: A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84-0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85-0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52-0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55-0.79). CONCLUSIONS: In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.

Paediatric distal radius fractures: an instructional review for the FRCS examination.

An instructional review of the literature and guidelines relevant for the classification, management and prognosis of paediatric distal radius fractures. Aimed at the knowledge level required for the trauma and orthopaedic FRCS examination.

Risk factors for perioperative blood transfusions after urogenital fistula repair in Uganda: a retrospective cohort study.

OBJECTIVE: To determine the incidence of and risk factors for perioperative blood transfusions after urogenital fistula repairs in Uganda. DESIGN: A retrospective cohort study. SETTING: A community hospital in Masaka, Uganda. POPULATION: Women who underwent fistula repair at the Kitovu Hospital between 2013 and 2019. METHODS: Retrospective review of demographics and clinical perioperative characteristics of patients surgically treated for urogenital fistula. Patient characteristics were compared between those who did and those who did not require a blood transfusion. MAIN OUTCOME MEASURES: Need for perioperative blood transfusion and risk factors. RESULTS: A total of 546 patients treated for urogenital fistulas were included in this study. The median age was 31.1 ± 13.2 years. A vaginal surgical approach was used in the majority of patients (84.6%). Complications occurred in 3.5% of surgical repairs, and the incidence of blood transfusions was 6.2%. In multivariable analyses, for each gram per deciliter (g/dl) increase in preoperative haemoglobin, the odds of blood transfusion decreased by approximately 28% (adjusted OR 0.72, 95% CI 0.59-0.86). Women who had their fistula repaired abdominally were 3.4 times more likely to require transfusions (95% CI 1.40-8.08). CONCLUSIONS: The incidence of blood transfusions among urogenital fistula repairs in our population is twice that of developed nations. An abdominal surgical approach to urogenital fistula is a significant risk factor for perioperative blood transfusions. The timing of the repair may warrant further study. TWEETABLE ABSTRACT: One of the first studies to look at blood transfusion risk factors after fistula repair in a low-resource setting.

The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage.RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen.CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

TGFß1 induces resistance of human lung myofibroblasts to cell death via down-regulation of TRPA1 channels.

BACKGROUND AND PURPOSE: TGFß1-mediated myofibroblast activation contributes to pathological fibrosis in many diseases including idiopathic pulmonary fibrosis (IPF), where myofibroblast resistance to oxidant-mediated apoptosis is also evident. We therefore investigated the involvement of redox-sensitive TRPA1 ion channels on human lung myofibroblasts (HLMFs) cell death and TGFß1-mediated pro-fibrotic responses. EXPERIMENTAL APPROACH: The effects of TGFß1 stimulation on TRPA1 expression and cell viability was studied in HLMFs derived from IPF patients and non-fibrotic patients. We also examined a model of TGFß1-dependent fibrogenesis in human lung. We used qRT-PCR, immunofluorescent assays, overexpression with lentiviral vectors and electrophysiological methods. KEY RESULTS: TRPA1 mRNA, protein and ion currents were expressed in HLMFs derived from both non-fibrotic patient controls and IPF patients, and expression was reduced by TGFß1. TRPA1 mRNA was also down-regulated by TGFß1 in a model of lung fibrogenesis in human lung. TRPA1 over-expression or activation induced HLMF apoptosis, and activation of TRPA1 channel activation by H2 O2 induced necrosis. TRPA1 inhibition following TGFß1 down-regulation or pharmacological inhibition, protected HLMFs from both apoptosis and necrosis. Lentiviral vector mediated TRPA1 expression was also found to induce sensitivity to H2 O2 induced cell death in a TRPA1-negative HEK293T cell line. CONCLUSION AND IMPLICATIONS: TGFß1 induces resistance of HLMFs to TRPA1 agonist- and H2 O2 -mediated cell death via down-regulation of TRPA1 channels. Our data suggest that therapeutic strategies which prevent TGFß1-dependent down-regulation of TRPA1 may reduce myofibroblast survival in IPF and therefore improve clinical outcomes.

First results from five multidisciplinary diagnostic centre (MDC) projects for non-specific but concerning symptoms, possibly indicative of cancer.

BACKGROUND: Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms. METHODS: The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings. RESULTS: In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP 'clinical suspicion' was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008). CONCLUSIONS: The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway.

Impact of choice of volumetry software and nodule management guidelines on recall rates in lung cancer screening.

PURPOSE: Appropriate lung nodule management is essential to minimizing unnecessary patient recall in lung cancer screening. Two European guidelines provide differing recommendations in that participants with nodules ≥100 mm3 or ≥80 mm3 respectively should be recalled, at baseline. Nodule size estimation is known to vary between volumetry software packages (VSPs). The aim of this study was to examine the impact of choice of VSP on participant recall rates, when applying different European nodule management guidelines. An additional aim was to compare recall rates between 7 VSPs and manual diameter measurements. METHODS: 156 small-sized lung nodules (50-150 mm3) from the UK Lung Screening trial were measured using 7 different VSPs (VSP1-7) and also using manual diameter. The type of VSP used in the NELSON study (VSP1), on which European nodule management guidelines are based, provided the reference standard. Nodule size was compared using Bland Altman, and recall rates by Mcnemar's test. RESULTS: Compared to the reference standard, a 100 mm3 threshold for recall, resulted in no difference in recall rates only for VSP 5 & 7. Using an 80mm3 threshold resulted in no difference in recall rates for VSP2 & 6. Recall rates were significantly higher for VSP 4 regardless of threshold and when using manual diameter measurements. CONCLUSIONS: Appropriate nodule size thresholds for recall in screening depend on the type of volumetry software used. The results highlight the importance of benchmarking of volumetry packages.

Final Results of the Prospective FH02 Mammographic Surveillance Study of Women Aged 35-39 at Increased Familial Risk of Breast Cancer.

BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40 years of age. There are almost no available data to assess whether mammography screening aged 35-39 years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8 years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2 cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293) ≤ 2 cm in POSH vs 80% (28/35) in FH02 p < 0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: p = 0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5 mGy. INTERPRETATION: Mammography screening aged 35-39 years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49 years.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

The impact of mammography screening programmes on incidence of advanced breast cancer in Europe: a literature review.

BACKGROUND: Observational studies have reported conflicting results on the impact of mammography service screening programmes on the advanced breast cancer rate (ABCR), a correlation that was firmly established in randomized controlled trials. We reviewed and summarized studies of the effect of service screening programmes in the European Union on ABCR and discussed their limitations. METHODS: The PubMed database was searched for English language studies published between 01-01-2000 and 01-06-2018. After inspection of titles and abstracts, 220 of the 8644 potentially eligible papers were considered relevant. Their abstracts were reviewed by groups of two authors using predefined criteria. Fifty studies were selected for full paper review, and 22 of these were eligible. A theoretical framework for their review was developed. Review was performed using a ten-point checklist of the methodological caveats in the analysis of studies of ABCR and a standardised assessment form designed to extract quantitative and qualitative information. RESULTS: Most of the evaluable studies support a reduction in ABCR following the introduction of screening. However, all studies were challenged by issues of design and analysis which could at least potentially cause bias, and showed considerable variation in the estimated effect. Problems were observed in duration of follow-up time, availability of reliable reference ABCR, definition of advanced stage, temporal variation in the proportion of unknown-stage cancers, and statistical approach. CONCLUSIONS: We conclude that much of the current controversy on the impact of service screening programmes on ABCR is due to observational data that were gathered and/or analysed with methodological approaches which could not capture stage effects in full. Future research on this important early indicator of screening effectiveness should focus on establishing consensus in the correct methodology.

The variation in chemical composition of barley feed with or without enzyme supplementation influences nutrient digestibility and subsequently affects performance in piglets.

This study investigates the effect of dietary supplementation of a ß-glucanase and ß-xylanase enzyme mix to barley based diets, at two different chemical compositions achieved through different agronomical conditions on growth performance, coefficient of apparent total tract digestibility (CATTD) of nutrients, selected faecal microbial populations and faecal scores in piglets. Sixty-four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one of four dietary treatments (n = 8). The dietary treatments were as follows: (T1) low quality barley diet, (T2) low quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement, (T3) high quality barley diet and (T4) high quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement. Piglets offered the low quality barley-based diet had a higher (p < .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F) ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral detergent fibre (NDF) compared with piglets offered the high quality barley diet. Piglets offered the high quality barley-based diet had reduced faecal scores compared to piglets offered the low quality barley-based diet (2.44 vs. 2.57, SEM 0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs. 10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001) in the faeces of piglets offered the high quality barley-based diet compared to piglets offered the low quality barley-based diet. The inclusion of a ß-glucanase and ß-xylanase enzyme complex had no effect on any variable measured. In conclusion, the higher quality barley-based diet showed beneficial effects on the faecal Lactobacillus spp. population and faecal scores of the piglets; however, the higher level of ß-glucans in the diet decreased nutrient digestibility and subsequently decreased the performance.

Review of Mechanical Testing and Modelling of Thrombus Material for Vascular Implant and Device Design.

A thrombus or blood clot is a solid mass, made up of a network of fibrin, platelets and other blood components. Blood clots can form through various pathways, for example as a result of exposed tissue factor from vascular injury, as a result of low flow/stasis, or in very high shear flow conditions. Embolization of cardiac or vascular originating blood clots, causing an occlusion of the neurovasculature, is the major cause of stroke and accounts for 85% of all stroke. With mechanical thrombectomy emerging as the new standard of care in the treatment of acute ischemic stroke (AIS), the need to generate a better understanding of the biomechanical properties and material behaviour of thrombus material has never been greater, as it could have many potential benefits for the analysis and performance of these treatment devices. Defining the material properties of a thrombus has obvious implications for the development of these treatment devices. However, to-date this definition has not been adequately established. While some experimentation has been performed, model development has been extremely limited. This paper reviews the previous literature on mechanical testing of thrombus material. It also explores the use of various constitutive and computational models to model thrombus formation and material behaviour.

Episodic memory in depression: the unique contribution of the anterior caudate and hippocampus.

BACKGROUND: Learning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus. METHOD: Eighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2, s.d. = 9.1 years) and 27 never-depressed control participants (mean age = 63.9, s.d. = 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods. RESULTS: Depressed subjects had smaller right anterior caudate (RAC) (t = 2.3, p = 0.026) and poorer memory compared to controls (t = 2.5, p < 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r = 0.3, p = 0.003) and older age (r = -0.46, p < 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (ß = 0.25, t = 2.16, p = 0.033; ß = 0.19, t = 1.71, p = 0.091). CONCLUSIONS: In older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI). AIM: We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor. METHODS: We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding. RESULTS: For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64). CONCLUSION: Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.