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Inflammation is thought to play a role in heart failure (HF) pathophysiology. Neutrophil-to-lymphocyte ratio (NLR) is a simple, routinely available measure of inflammation. Its relationship with other inflammatory biomarkers and its association with clinical outcomes in addition to other risk markers have not been comprehensively evaluated in HF patients.\ud \ud Methods\ud We evaluated patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available NLR at baseline. The primary outcome was time to all-cause mortality or HF hospitalization. Outcomes were validated in a separate HF population.\ud \ud Results\ud 1622 patients were evaluated (including 523 ventricular ejection fraction [LVEF] < 40% and 662 LVEF ≥ 40%). NLR was significantly correlated with biomarkers related to inflammation as well as NT-proBNP. NLR was significantly associated with the primary outcome in patients irrespective of LVEF (hazard ratio [HR] 1.18 per standard deviation increase; 95% confidence interval [CI] 1.11–1.26, P < 0.001). Patients with NLR in the highest tertile had significantly worse outcome than those in the lowest independent of LVEF (

Cardiovascular MRI has become an essential imaging modality in children with congenital heart disease (CHD) in the last 15–20 years. With use of appropriate sequences, it provides important information on cardiovascular anatomy, blood flow and function for initial diagnosis and post-surgical or -interventional monitoring in children. Although considered as more sophisticated and challenging than CT, in particular in neonates and infants, MRI is able to provide information on intra- and extracardiac haemodynamics, in contrast to CT. In recent years, four-dimensional (4-D) flow MRI has emerged as an additional MR technique for retrospective assessment and visualisation of blood flow within the heart and any vessel of interest within the acquired three-dimensional (3-D) volume. Its application in young children requires special adaptations for the smaller vessel size and faster heart rate compared to adolescents or adults. In this article, we provide an overview of 4-D flow MRI in various types of complex CHD in neonates and infants to demonstrate its potential indications and beneficial application for optimised individual cardiovascular assessment. We focus on its application in clinical routine cardiovascular workup and, in addition, show some examples with pathologies other than CHD to highlight that 4-D flow MRI yields new insights in disease understanding and therapy planning. We shortly review the essentials of 4-D flow data acquisition, pre- and post-processing techniques in neonates, infants and young children. Finally, we conclude with some details on accuracy, limitations and pitfalls of the technique. Electronic supplementary material The online version of this article (10.1007/s00247-020-04885-w) contains supplementary material, which is available to authorized users.

Objectives To use 4D-flow MRI to describe systemic and non-systemic ventricular flow organisation and energy loss in patients with repaired d-transposition of the great arteries (d-TGA) and normal subjects. Methods Pathline tracking of ventricular volumes was performed using 4D-flow MRI data from a 1.5-T GE Discovery MR450 scanner. D-TGA patients following arterial switch (n = 17, mean age 14 ± 5 years) and atrial switch (n = 15, 35 ± 6 years) procedures were examined and compared with subjects with normal cardiac anatomy and ventricular function (n = 12, 12 ± 3 years). Pathlines were classified by their passage through the ventricles as direct flow, retained inflow, delayed ejection flow, and residual volume and visually and quantitatively assessed. Additionally, viscous energy losses (ELv) were calculated. Results In normal subjects, the ventricular flow paths were well ordered following similar trajectories through the ventricles with very little mixing of flow components. The flow paths in all atrial and some arterial switch patients were more irregular with high mixing. Direct flow and delayed ejection flow were decreased in atrial switch patients’ systemic ventricles with a corresponding increase in residual volume compared with normal subjects (p = 0.003 and p < 0.001 respectively) and arterial switch patients (p < 0.0001 and p < 0.001 respectively). In non-systemic ventricles, arterial switch patients had increased direct flow and decreased delayed ejection fractions compared to normal (p = 0.007 and p < 0.001 respectively) and atrial switch patients (p = 0.01 and p < 0.001 respectively). Regions of high levels of mixing of ventricular flow components showed elevated ELv. Conclusions 4D-flow MRI pathline tracking reveals disordered ventricular flow patterns and associated ELv in d-TGA patients. Key Points • 4D-flow MRI can be used to assess intraventricular flow dynamics in d-TGA patients. • d-TGA arterial switch patients mostly show intraventricular flow dynamics representative of normal subjects, while atrial switch patients show increased flow disorder and different proportions of intraventricular flow volumes. • Flow disruption and disorder increase viscous energy losses.

Funding Acknowledgements Type of funding sources: None. Purpose We sought to retrospectively evaluate the feasibility of identifying the fetal cardiac and thoracic vascular structures with non-gated dynamic balanced steady-state free precession MRI sequences. Methods We retrospectively assessed the visibility of cardiovascular anatomy in 66 fetuses without suspicion of congenital heart defect (mean gestational age 27+/- 4, range 21-38 weeks). Non-gated dynamic balanced steady-state free precession (SSFP) sequences were acquired in three planes (axial, coronal and sagittal) of the fetal thorax (slice thickness 4-5mm, FOV 400, FA 60°, matrix 256x256). The images were analysed following a segmental approach in consensus reading by an experienced paediatric cardiologist and radiologist. An imaging score was defined by giving one point to each visualized structure. Basic diagnostic structures included the atria, ventricles, systemic veins, right and left ventricular outflow tracts (RVOT/LVOT), aortic arch, descending aorta (DAO), ductus arteriosus and thymus (12 points); advanced diagnostic features included the atrioventricular (AV) valves, pulmonary arteries and veins, supraaortic arteries and trachea, yielding a maximum score of 21 points. Image quality was rated from 0 (poor) to 2 (good). The influence of gestational age (GA), field strength, placenta position, and maternal panniculus on image quality and imaging score were tested. Results 34 scans were performed at 1.5 T, 32 at 3 T. Heart position, atria and ventricles could be seen in all 66 fetuses. Basic diagnosis (>12 points) was achieved in 60 (90%) cases, with visualization of the IVC and SVC in 65 (98%) and 63 (95%), RVOT in 62 (94%), LVOT in 61 (92%), aortic arch in 60 (91%), DAO in 64 (97%), ductus arteriosus in 59 (89%) and thymus in 50 (76%) fetuses. The AV valves were recognised in 55 (83%), the pulmonary arteries in 35 (53%), at least one pulmonary vein in 46 (70%), the supraaortic arteries in 42 (64%), and the trachea in 59 (89%) fetuses. The mean imaging score was 16.8 +/- 3.7. Maternal panniculus (r -0.3; p 0.01) and gestational age (r 0.6; p < 0.001) correlated with imaging score. Field strength influenced image quality, with 1.5 T being better than 3T images (p 0.04), but not the total imaging score. Imaging score or quality were independent from placenta position. Conclusions Fetal heart MRI with a non-gated SSFP sequence in multiple planes enables recognition of basic cardiovascular anatomy. Advanced diagnostics may be limited by thick maternal panniculus, lower GA and higher field strength.

The global pandemic of COVID-19 has challenged the management of hypoxaemic respiratory failure and strained intensive care unit resources. While prone positioning (PP) is an established therapy in mechanically ventilated patients with acute respiratory distress syndrome (ARDS), its role in conscious patients is less well defined. We retrospectively reviewed our experience of implementing early PP in a cohort of 24 patients with acute hypoxaemic respiratory failure due to COVID-19 who required support with continuous positive airway pressure (CPAP). The use of PP alongside CPAP significantly increased both the ROX index and arterial oxygen pressure:fractional inspired oxygen (PaO2:FiO2) ratio from baseline values (ROX index: 7.0±2.5 baseline vs 11.4±3.7 CPAP+PP, p2:FiO2 ratio: 143±73 mm Hg baseline vs 252±87 mm Hg CPAP+PP, p2:FiO2 ratio remained significant 1 hour after cessation of proning. The mean duration of PP in the first 24 hours was 8±5 hours. Few complications were observed and PP was continued for a mean of 10±5 days. From our experience in a dedicated COVID-19 respiratory high care unit, PP alongside CPAP therapy was feasible, tolerated, safe and improved oxygenation. The use of conscious PP in ARDS warrants further investigation in randomised controlled trials.

Treatment of heart failure with preserved ejection fraction (HFpEF) remains a major unmet medical need. An implantable valveless pulsatile pump with a single cannula—the CoPulse pump—may provide beneficial hemodynamic support for select HFpEF patients when connected to the failing ventricle. We aimed to demonstrate hemodynamic efficacy and hemocompatible design feasibility for this novel assist device. The hemodynamic effect of the pump was investigated with an in vitro circulatory mock loop and an ex vivo isolated porcine heart model. The hydraulic design was optimized using computational fluid dynamics (CFD), and validated by 4D-flow magnetic resonance imaging (MRI). The pump reduced left atrial pressure (> 27%) and increased cardiac output (> 14%) in vitro. Ex vivo experiments revealed elevated total stroke volume at increased end-systolic volume during pump support. Asymmetric cannula positioning indicated superior washout, decreased stagnation (8.06 mm2 vs. 31.42 mm2), and marginal blood trauma potential with moderate shear stresses ( 0.76). The CoPulse pump proved hemodynamically effective. Hemocompatibility metrics were comparable to those of a previously reported, typical pulsatile pump with two cannulae. The encouraging in vitro, ex vivo, and hemocompatibility results substantiate further development of the CoPulse pump., Annals of Biomedical Engineering, 48, ISSN:1573-9686, ISSN:0191-5649, ISSN:0090-6964

Background Abnormal flow dynamics play an early and causative role in pathologic changes of the ascending aorta. Purpose To identify: 1) the changes in flow, shape, and size that occur in the ascending aorta with normal human ageing and 2) the influence of these factors on aortic flow dynamics. Study type Retrospective. Subjects In all, 247 subjects (age range 19-86 years, mean 49 ± 17.7, 169 males) free of aortic or aortic valve pathology were included in this study. Subjects were stratified by youngest (18-33 years; n = 64), highest (>60 years, n = 67), and the middle two quartiles (34-60 years, n = 116). Field strength/sequence Subjects underwent a cardiac MRI (3T) exam including 4D-flow MRI of the aorta. Assessment Aortic curvature, arch shape, ascending aortic angle, ascending aortic diameter, and the stroke volume normalized by the aortic volume (nSV) were measured. Velocity, vorticity, and helicity were quantified across the thoracic aorta. Statistical tests Univariate and multivariate regressions were used to quantify continuous relationships between variables. Results Aortic diameter, ascending aortic angle, shape, and curvature all increased across age while nSV decreased (all P 10 times that of diameter and other shape factors. Data conclusion Aortic shape influences flow dynamics in younger subjects. Flow conditions become increasingly disturbed with advancing age, and in these conditions nSV has a more dominant effect on flow patterns than shape factors. Level of evidence 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:90-100.

BackgroundThere is limited evidence on the prevalence and identification of antenatal mental disorders.AimsTo investigate the prevalence of mental disorders in early pregnancy and the diagnostic accuracy of depression-screening (Whooley) questions compared with the Edinburgh Postnatal Depression Scale (EPDS), against the Structured Clinical Interview DSM-IV-TR.MethodCross-sectional survey of women responding to Whooley questions asked at their first antenatal appointment. Women responding positively and a random sample of women responding negatively were invited to participate.ResultsPopulation prevalence was 27% (95% CI 22–32): 11% (95% CI 8–14) depression; 15% (95% CI 11–19) anxiety disorders; 2% (95% CI 1–4) obsessive–compulsive disorder; 0.8% (95% CI 0–1) post-traumatic stress disorder; 2% (95% CI 0.4–3) eating disorders; 0.3% (95% CI 0.1–1) bipolar disorder I, 0.3% (95% CI 0.1–1%) bipolar disorder II; 0.7% (95% CI 0–1) borderline personality disorder. For identification of depression, likelihood ratios were 8.2 (Whooley) and 9.8 (EPDS). Diagnostic accuracy was similar in identifying any disorder (likelihood ratios 5.8 and 6).ConclusionsEndorsement of Whooley questions in pregnancy indicates the need for a clinical assessment of diagnosis and could be implemented when maternity professionals have been appropriately trained on how to ask the questions sensitively, in settings where a clear referral and care pathway is available.Declaration of interestL.M.H. chaired the National Institute for Health and Care Excellence CG192 guidelines development group on antenatal and postnatal mental health in 2012–2014.

Background In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. Methods This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. Results During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). Conclusions and implications for public health practice These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

Peripheral veno-arterial extra-corporeal membrane oxygenation (ECMO) is an artificial circulation that supports patients with severe cardiac and respiratory failure. Differential hypoxia during ECMO support has been reported, and it has been suggested that it is due to the mixing of well-perfused retrograde ECMO flow and poorly-perfused antegrade left ventricle (LV) flow in the aorta. This study aims to quantify the relationship between ECMO support level and location of the mixing zone (MZ) of the ECMO and LV flows. Steady-state and transient computational fluid dynamics (CFD) simulations were performed using a patient-specific geometrical model of the aorta. A range of ECMO support levels (from 5% to 95% of total cardiac output) were evaluated. For ECMO support levels above 70%, the MZ was located in the aortic arch, resulting in perfusion of the arch branches with poorly perfused LV flow. The MZ location was stable over the cardiac cycle for high ECMO flows (>70%), but moved 5cm between systole and diastole for ECMO support level of 60%. This CFD approach has potential to improve individual patient care and ECMO design.

Imaging-based evaluation of cardiac structure and function remains paramount in the diagnosis and monitoring of congenital heart disease in childhood. Accurate measurements of intra- and extracardiac hemodynamics are required to inform decision making, allowing planned timing of interventions prior to deterioration of cardiac function. Four-dimensional flow magnetic resonance imaging is a nonionizing noninvasive technology that allows accurate and reproducible delineation of blood flow at any anatomical location within the imaging volume of interest, and also permits derivation of physiological parameters such as kinetic energy and wall shear stress. Four-dimensional flow is the focus of a great deal of attention in adult medicine, however, the translation of this imaging technique into the pediatric population has been limited to date. A more broad-scaled application of 4-dimensional flow in pediatric congenital heart disease stands to increase our fundamental understanding of the cause and significance of abnormal blood flow patterns, may improve risk stratification, and inform the design and use of surgical and percutaneous correction techniques. This paper seeks to outline the application of 4-dimensional flow in the assessment and management of the pediatric population affected by congenital heart disease.

Current standards and best practice guidance recognise that testing of self-drilled hollow bar soil nails can be problematic as conventional packers and debonded lengths cannot be constructed. As a result, this causes difficulty in testing and confirming the ultimate bond resistance within the passive zone of a soil-nailed slope, and thus the design soil nail lengths. This paper provides a summary and review of the various testing procedures adopted for a soil nail construction project in Scotland. The practical design considerations, and their validation through the installation and testing of 49 sacrificial test nails, are detailed. The construction issues associated with the nail installation and testing are also outlined and discussed in light of the results obtained using different testing approaches. The aim of this case study is to report on the experiences with installation and testing of hollow bar soil nails. The objectives are to develop an initial data base of available soil–grout bond strength of hollow bar soil nails based on the several practical installation procedures used in this project and to establish areas for improvement of installation, testing and quality control in order to perform comparable pullout tests on self-drilled hollow bar soil nails.

PURPOSE 4D-flow MRI obtains a time-dependent 3D velocity field; however, its use for the calculation of higher-order parameters is limited by noise. We present an algorithm for denoising 4D-flow data. THEORY AND METHODS By integrating a velocity field and eliminating streamlines in noisy flow, depicted by high curvature, a denoised dataset may be extracted. This method, defined as the velocity field improvement (VFIT) algorithm, was validated in an analytical dataset and using in vivo data in comparison with a computation fluid dynamics (CFD) simulation. As a proof of principal, wall shear stress (WSS) measurements in the descending aorta were compared with those defined by CFD. RESULTS The VFIT algorithm achieved a >100% noise reduction of a corrupted analytical dataset. In addition, 4D-flow data were cleaned to show improved spatial resolution and near wall velocity representation. WSS measures compared well with CFD data and bulk flow dynamics were retained (

Introduction It is increasingly recognised that inflammation plays an important role in the pathogenesis and progression of heart failure (HF) and may have important therapeutic and diagnostic implications. Research has shown that raised inflammatory cytokines are associated with adverse outcomes, however these are not routinely assessed in clinical practice. The aim of this study was to evaluate the association of neutrophil to lymphocyte ratio (NLR), a simple, routinely-measured parameter of inflammatory status, with prognostic outcomes in a cohort of HF patients. Methods Patients who had survived to 30 days or discharge following an initial HF hospitalisation from the Genetics of Diabetes and Audit Research Tayside Scotland (GoDARTS) study were included. Baseline clinical and demographic data were obtained from electronic health records. Patients with available echocardiography were used to perform a stratified analysis (HFrEF – ejection fraction Results In total 1,157 patients with HF were included (mean age 73 years, 61.7% male, 740 HFrEF, 417 HFpEF), 847 reached primary outcome (713 deaths and 471 HF admissions). Median follow-up was 769 days. In multivariable analysis (adjusting for blood-pressure, cholesterol, age, gender, diabetes and smoking status) higher NLR at the time of HF diagnosis was significantly associated with the primary outcome (HR 1.04; 95% CI 1.02–1.05, p Conclusion We found that NLR, a simple measure of inflammation was significantly associated with prognosis in HFrEF and HFpEF. These results support the growing consensus that inflammation plays a key role in HF. Future research should focus on comparing the NLR with established markers in HF, and the potential use of anti-inflammatory interventions targeting NLR in the treatment of HF. Kaplan-Meier curves of the association between NLR Tertiles and the primary outcome in HFpEF and HFrEF: Conflict of Interest No

Background In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth.Methods We updated search results of a recent systematic review by searching MEDLINE and Embase from Jan 1,2016, to May 5,2017, and used expert knowledge to identify published studies reporting on local regrowth in patients with rectal cancer managed by watch and wait after clinical complete response to neoadjuvant chemoradiotherapy. We restricted studies to those that defined clinical complete response using criteria equivalent to Sao Paulo benchmarks (ie, absence of residual ulceration, stenosis, or mass within the rectum on clinical and endoscopic examination). The primary outcome was 2-year cumulative incidence of local regrowth, estimated with a two-stage random-effects individual participant data meta-analysis. We assessed the effects of clinical and treatment factors using Cox frailty models, expressed as hazard ratios (HRs). From these models, we derived percentage differences in mean 0 as an approximation of the effect of measured covariates on between-centre heterogeneity. This study is registered with PROSPERO, number CRD42017070934.Findings We obtained individual participant data from 11 studies, including 602 patients enrolled between March 11,1990, and Feb 13, 2017, with a median follow-up of 37.6 months (IQR 25.0-58.7). Ten of the 11 datasets were judged to be at low risk of bias. 2-year cumulative incidence of local regrowth was 21.4% (random-effects 95% CI 15.3-27.6), with high levels of between-study heterogeneity (I 2 =61%). We noted wide between-centre variation in patient, tumour, and treatment characteristics. We found some evidence that increasing cT stage was associated with increased risk of local regrowth (random-effects HR per cT stage 1.40, 95% CI 1.00-1.94; P-trend=0. 048). In a subgroup of 459 patients managed after 2008 (when pretreatment staging by MRI became standard), 2-year cumulative incidence of local regrowth was 19% (95% CI 13-28) for stage cT1 and cT2 tumours, 31% (26-37) for cT3, and 37% (21-60) for cT4 (random-effects HR per cT stage 1.50, random-effects 95% CI 1.03-247; P-trend=0. 0330). We estimated that measured factors contributed 4.8-45-3% of observed between-centre heterogeneity.Interpretation In patients with rectal cancer and clinical complete response after chemoradiotherapy managed by watch and wait, we found some evidence that increasing cT stage predicts for local regrowth. These data will inform clinician-patient decision making in this setting. Research is needed to determine other predictors of a sustained clinical complete response. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

What you need to know Colorectal cancer is the third commonest cancer worldwide.1 About a third of these arise in the rectum. Approximately a third of rectal cancers are locally advanced and at high risk of recurrence. Long-course chemoradiotherapy followed by surgical resection is now standard treatment for these tumours in the UK,23 Europe,4 the US,5 and Australia.6 However, surgery is associated with major complications (up to 15%), perioperative mortality (up to 5%), and the need for a permanent stoma in up to a quarter of patients.7 Within the published literature, after chemoradiotherapy 10-25% of patients have no residual tumour on pathological examination after surgical resection.78910 Clinical examination before surgery in these patients has shown an equivalent favourable response, referred to as a clinical complete response. The criteria for defining a clinical complete response include absence of residual ulceration, stenosis, or mass within the rectum during digital rectal examination and endoscopic examination (fig 1).910 Fig 1 Endoscopic images of rectum after chemoradiotherapy for rectal cancer show (A) “white” scar (circled) and (B) telangiectasia changes (arrow). Both are accepted as “normal” and are compatible with a clinical complete response Nearly 15 years ago, a seminal study from a centre in Sao Paulo, Brazil reported that 71 patients with clinical complete response were managed without initial surgery. Instead they were managed by a non-surgical “watch-and-wait” …

Purpose To investigate the association between childhood maltreatment and adulthood domestic and sexual violence victimisation among people with severe mental illness (SMI), and to explore this association in terms of gender differences and potential mediators.Method A cross-sectional survey of 318 people living in the community who were receiving care from Community Mental Health Teams. Associations were assessed using logistic regression of multiply imputed data.Results 63 % (95 % CI 55–71 %) of men and 71 % (95 % CI 63–79 %) of women reported childhood maltreatment,46 % (95 % CI 37–54 %) of men and 67 % (95 % CI 59–76 %) of women reported adulthood domestic violence victimisation, and 22 % (95 % CI 15–28 %)of men and 62 % (95 % CI 53–70 %)of women reported adulthood sexual violence victimisation. Men and women with SMI who reported experiences of childhood maltreatment were two to five times more likely to report domestic and sexual violence victimisation in adulthood after adjusting for confounders. The associations held for each of emotional,physical and sexual childhood abuse.Conclusion People with severe mental illness have high prevalence of experiences of childhood maltreatment and adulthood domestic and sexual violence victimisation.Childhood maltreatment appears to be an independent risk factor for adulthood victimisation among men and women with SMI.

OBJECTIVE There is limited evidence on the prevalence and odds of antenatal common mental disorders (CMDs) among migrant women and the effect on risk of intersecting variables such as immigration status and ethnicity. This study aimed to estimate the prevalence and odds of antenatal CMDs among migrant women compared to UK-born women in an inner-London maternity service. METHODS A cross-sectional survey stratified by response to depression screening questions was administered at first antenatal appointment. CMDs were assessed using the Structured Clinical Interview for DSM-IV. Recruitment took place between November 2014 and June 2016. RESULTS Prevalence of antenatal CMDs was 21% (95% CI, 16-28) among migrant women (n = 283) and 24% (95% CI, 18-31) among UK-born women (n = 262). There was no significant difference in the odds of CMDs among migrant women compared to UK-born women (OR = 0.86; P = .57; 95% CI, 0.51-1.44). Migrant women, particularly those with insecure immigration status, had increased odds of posttraumatic stress disorder (OR = 29.08; P < .01; 95% CI, 4-188). When analyses were stratified by ethnicity, there was no effect of migrant status for white women, but for ethnic minority (nonwhite) women, migrant status decreased odds of having a CMD (OR = 0.31; P = .02; 95% CI, 0.12-0.82). CONCLUSIONS Antenatal common mental disorders are prevalent among migrant women, but migrant status is unlikely to increase risk on its own. Immigration status, ethnicity, and other intersecting variables of social disadvantage must be investigated simultaneously to examine the perinatal mental health of heterogeneous migrant populations.

Peripheral veno-arterial extra corporeal membrane oxygenation (VA-ECMO) is an established technique for short-to-medium support of patients with severe cardiac failure. However, in patients with concomitant respiratory failure, the residual native circulation will provide deoxygenated blood to the upper body, and may cause differential hypoxemia of the heart and brain. In this paper, we present a general computational framework for the identification of differential hypoxemia risk in VA-ECMO patients. A range of different VA-ECMO patient scenarios for a patient-specific geometry and vascular resistance were simulated using transient computational fluid dynamics simulations, representing a clinically relevant range of values of stroke volume and ECMO flow. For this patient, regardless of ECMO flow rate, left ventricular stroke volumes greater than 28 mL resulted in all aortic arch branch vessels being perfused by poorly-oxygenated systemic blood sourced from the lungs. The brachiocephalic artery perfusion was almost entirely derived from blood from the left ventricle in all scenarios except for those with stroke volumes less than 5 mL. Our model therefore predicted a strong risk of differential hypoxemia in nearly all situations with some residual cardiac function for this combination of patient geometry and vascular resistance. This simulation highlights the potential value of modelling for optimising ECMO design and procedures, and for the practical utility for personalised approaches in the clinical use of ECMO.

Background:\ud Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management.\ud \ud Methods:\ud This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane between baseline and 12 months. Secondary outcomes include patient-reported outcomes and several structural and biomechanical measures relevant to the pathogenesis of FAI and development of hip OA. Interventions will be compared by intention-to-treat analysis.\ud \ud Discussion:\ud The findings will help determine whether hip arthroscopy or an individualised physiotherapy program is superior for the management of FAI, including for the prevention of hip OA.\ud \ud Trial registration:\ud Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549. Trial registered 2/11/2015 (retrospectively registered).

Background: Chronic descending thoracic aortic dissection (CDTAD) following surgical repair of ascending aortic dissection requires long-term imaging surveillance. We investigated four-dimensional (4D)-flow magnetic resonance imaging (MRI) with a novel multi-velocity encoding (multi-VENC) technique as an emerging clinical method enabling the dynamic quantification of blood volume and velocity throughout the cardiac cycle. Methods: Patients with CDTAD (n = 10; mean age, 55.1 years; standard deviation (SD) 10.8) and healthy volunteers (n = 9; mean age, 37.1 years; SD 11.4; p < 0.01) underwent 3T MRI, and standard views and 4D-flow data were obtained. Flow measurements were made in selected regions of interest within the ascending and descending thoracic aorta. Results: The overall flow profile at peak systole was reduced in the false lumen (FL) compared with the true lumen (TL) and normal aortas (p < 0.05 for velocity < 0.4 m/s). Peak systolic flow rate per aortic lumen area (mL/s/cm2) was lower in the FL than in the TL (p < 0.05), and both rates were lower than that of control aortas (p < 0.05). Blood flow reversal was higher in the FL than in the TL throughout the descending aorta in CDTAD patients (p < 0.05). A derived pulsatility index was elevated in the TL compared with that in the FL in CDTAD patients. Generated pathline images demonstrated flow patterns in detail, including sites of communication between the true and FL. Conclusions: 4D-flow MRI revealed FL blood flow and reduced blood flow velocity and flow rate in the TL of CDTAD patients compared with normal aortas of healthy participants. Thus, multi-VENC 4D-flow MRI could serve as an adjunct in the long-term assessment of CDTAD following surgical repair of ascending aortic dissection.

Aim The aim of this study was to determine the distribution of residual tumour within the bowel wall in relation to residual mucosal abnormalities (RMAs) and surrounding normal mucosa in patients with rectal cancer who underwent neoadjuvant chemoradiation followed by curative surgery. Method Archived pathological slides from a cohort of 60 patients with residual tumour were retrieved. The incidence, distance and depth of tumour spread (ypT) under RMAs and adjacent normal mucosa were reviewed and recorded. Results Histological sections containing both RMA and adjacent normal mucosa were available for 45 of 60 patients with ypT1 (n = 6), ypT2 (n = 18) and ypT3 (n = 21) disease. The maximal depth of invasion, as measured by ypT stage, was found underneath the RMA in 44 of 45 (98%) patients. Microscopic tumour spread lateral to the RMA and under adjacent normal mucosa was found in 32 of 45 (71%) patients. The median and maximum distances of lateral spread for ypT1 tumours were 0 and 4 mm; for ypT2 were 2.5 and 9 mm; and for ypT3 were 4 and 9 mm respectively. Conclusion Lateral tumour spread under normal mucosa adjacent to RMAs is a common finding and extended up to 9 mm in this study. The epicentre for maximum depth of invasion was directly underneath the RMAs in nearly all cases. These data have clinical and technical implications if local excision is to be considered.

Published criteria define specific mucosal features of clinical complete response for rectal cancer after neoadjuvant chemoradiotherapy.The aim of this study was to determine the performance of these criteria to identify a pathological complete response.Histopathology reports were retrieved for consecutive rectal cancers treated with neoadjuvant therapy followed by proctectomy. The mucosal appearance of residual disease was compared with the final pathological stage.This study was conducted at a single-institution, tertiary referral center.The study included 238 patients.All patients underwent neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007.Gross mucosal appearance was compared with the final pathological stage.Following neoadjuvant chemoradiation, 61 of 238 (25%) patients were downstaged to ypT0. Forty-five of these 61 patients (74%) had a residual mucosal abnormality that precluded assignment of a complete response. Of these, 40 had residual ulcers (up to 10 mm in depth) and 5 had exophytic lesions. The remaining 16 patients with pathological complete response fulfilled criteria for clinical complete response and had either no visible abnormality or a scar. Although mucosal complete clinical response was statistically associated with ypT0 status (p0.0001), 6 of 22 (27%) patients with mucosal complete clinical response still had residual disease. Smaller size of residual mucosal abnormality was also associated with ypT0 status (p = 0.002).This is a retrospective study and preoperative clinical assessment of response is not recorded for comparison to resected specimens.The majority of patients attaining ypT0 status do not display mucosal features of complete response. When present, a mucosal complete response is statistically associated with ypT0 status, but is poorly sensitive. If rectal conservation after chemoradiation is to be pursued, alternative means of restaging are required to maximize the number who might benefit from this approach.

Background Diastolic dysfunction is a major cause of morbidity in obese individuals. We aimed to assess the ability of magnetic resonance imaging (MRI) derived left atrial (LA) strain to detect early diastolic dysfunction in individuals with obesity and type 2 diabetes, and to explore the association between cardiac adipose tissue and LA function. Methods Twenty patients with obesity and T2D (55 ± 8 years) and nineteen healthy controls (48 ± 13 years) were imaged using cine steady state free precession and 2-point Dixon cardiovascular magnetic resonance. LA function was quantified using a feature tracking technique with definition of phasic longitudinal strain and strain rates, as well as radial motion fraction and radial velocities. Results Systolic left ventricular size and function were similar between the obesity and type 2 diabetes and control groups by MRI. All patients except four had normal diastolic assessment by echocardiography. In contrast, measures of LA function using magnetic resonance feature tracking were uniformly altered in the obesity and type 2 diabetes group only. Although there was no significant difference in intra-myocardial fat fraction, Dixon 3D epicardial fat volume(EFV) was significantly elevated in the obesity and type 2 diabetes versus control group (135 ± 31 vs. 90 ± 30 mL/m2, p Conclusions LA MRI-strain may be a sensitive tool for the detection of early diastolic dysfunction in individuals with obesity and type 2 diabetes and correlated with BMI and epicardial fat supporting a possible association between adiposity and LA strain. Trials Registration Australian New Zealand Clinical Trials Registry No. ACTRN12613001069741

Background The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. Methods We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. Results Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P = 0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P = 0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P = 0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P Conclusions In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

In light of an increasing intent by the UK Government to authorise hydraulic fracturing (also commonly known as ‘fracking’), this paper examines the experience of the U.S. in regulating a practice which presents considerable risk to the environment. The impact of shale gas development on water resources in particular has shaped the greatest regulatory response in U.S. states and is therefore the focus of this contribution. With the development cycle posing impacts on water use, groundwater and surface water contamination, this paper aims to assess how effectively the law in the U.S. is mitigating these risks both at federal and state level.From an assessment of U.S. regulation, the paper attempts to highlight areas from which the UK could learn and adjust its own existing legal framework in order to better protect against the presented water risks posed by a UK shale gas industry. Whilst the UK has existing general legislation in place, it has yet to reach production levels as experienced in the U.S. and this paper examines how the U.S. has been forced to adapt water law and policy during active shale gas development.The paper first explains and questions the U.S. decision to exempt fracking from the Safe Drinking Water Act, a uniform federal regulation. It argues that the rationale for the exemption is unsatisfactory and submits that a similar reactive policy towards water law must be avoided by UK Governments. As a result of the exemption, this paper then assesses the efforts made by regulators of the two leading shale gas producing states; namely Pennsylvania and Texas, to protect water resources. It first highlights how both states have controlled the use of water before fracking takes place by comparing common law doctrines and public body governance. Second, it assesses how both states have been forced to adapt existing well construction requirements to protect groundwater during fracking. The analysis of state regulation concludes by highlighting the problems of current federal regulation over the treatment of untreated wastewaters, and how Pennsylvania has been forced to amend its law in response to water contamination.The final section offers a preliminary overview of the current UK legal framework applying to shale gas and the risks to water resources. It offers an initial assessment as to whether the UK should consider adapting its water law in light of the U.S. experience. This assessment concludes that whilst the existing UK legislation is to some extent more advanced than its American counterpart, its effectiveness ultimately remains untested and a revisit of the existing regulation is recommended.

Spontaneous dissection of the cervical internal carotid artery (sICAD) is a major cause of stroke in young adults. A tear in the inner part of the vessel wall triggers sICAD as it allows the blood to enter the wall and develop a transmural hematoma. The etiology of the tear is unknown but many patients with sICAD report an initiating trivial trauma. We thus hypothesised that the site of the tear might correspond with the location of maximal stress in the carotid wall. Carotid artery geometries segmented from magnetic resonance images of a healthy subject at different static head positions were used to define a path of motion and deformation of the right cervical internal carotid artery (ICA). Maximum head rotation to the left and rotation to the left combined with hyperextension of the neck were investigated using a structural finite element model. A role of the carotid sinus as a geometrically compliant feature accommodating extension of the artery is shown. At the extreme range of the movements, the geometrical compliance of the carotid sinus is limited and significant stress concentrations appear just distal to the sinus with peak stresses at the internal wall on the posterior side of the vessel following maximum head rotation and on the anteromedial portion of the vessel wall following rotation and hyperextension. Clinically, the location of sICAD initiation is 10-30 mm distal to the origin of the cervical ICA, which corresponds with the peak stress locations observed in the model, thus supporting trivial trauma from natural head movements as a possible initiating factor in sICAD.

Neoadjuvant radiochemotherapy (RCT), followed by rectal cancer resection encompassing a total mesorectal excision, is increasingly accepted as the gold standard for patients with clinical T3/T4 rectal tumors.1–4 Compared with adjuvant regimens, neoadjuvant approaches are associated with a reduced rate of local recurrence and improved overall survival.2,5–10 The benefit of neoadjuvant therapy is most marked where a complete pathologic response (pCR) is achieved. Currently, approximately 10% to 30% of patients undergo pCR, characterized by complete sterilization of all tumor cells in the resected surgical specimen.11,12 The remainder demonstrate a spectrum of residual disease varying from a few scattered tumor cells to large islands of radioresistant tumor cells.13 It is not understood why tumors of identical pretreatment stage, undergoing identical neoadjuvant regimens, respond differently to RCT; therefore, all patients undergo empirical treatment. Moreover, RCT is expensive and time-consuming and increases both the perioperative morbidity and the risk of developing secondary tumors.4,14–16 The ability to identify and select only patients sensitive to or resistant to RCT, ideally before or in the early stages of treatment, would confer a major clinical advance, both in terms of the optimization of current treatment regimens, and the development of clinical trials. A further potential value for response predictors is highlighted by a recent seminal publication by Habr-Gama et al.17 In this study, patients with rectal cancer who underwent a complete clinical response to RCT were managed by observation alone rather than surgery. This cohort had lower rates of local recurrence and increased 5-year survival compared with patients with residual disease that underwent surgery. In this study, clinical assessment did not truly reflect pathologic response as 8.3% of patients deemed incomplete responders were found to have undergone pCR and a further 23% had pT1 disease. The inaccuracy of clinical response in predicting pathologic response has been identified in several other published reports.18,19 Identification of accurate means of response prediction using molecular markers would enable the true utility and benefits of conservative management after RCT to be evaluated. Furthermore, while the concept of conservative management after RCT has not previously been described for locally advanced rectal cancer, it is now an established first-line management in other malignancies such as squamous carcinoma of the anus.20,21 In recent years, the need for predictive markers to guide therapy, coupled with an increasing knowledge of molecular medicine, has prompted the analysis of archival pretreatment tumor biopsies from patients undergoing RCT. This work, to date, has mainly focused on identifying inherent molecular differences between good and poor responders using immunohistochemistry (IHC). The majority of studies have focused on single or small groups of molecular targets, most commonly mutations in the p53 gene or its downstream effector molecules. Results from these studies, however, have been largely inconclusive and still no clinically useful marker has been described.22,23 In recent months, Ghadimi et al reported on global gene expression profiles derived from fresh pretreatment rectal cancer biopsies using cDNA microarrays.24 In this case, a combination of 54 genes was identified, which showed significantly different expression in the pretreatment biopsy tissues of good versus poor responders. The ability for the combination of these genes to predict response was then assessed using leave-one-out cross-validation. Tumor behavior was correctly predicted on an individual patient basis with 78% sensitivity and 80% specificity. This study is important, as it is the first in rectal cancer to predict response on an individual patient basis using genomic profiling, an approach that may more accurately reflect the multiplicity of pathways controlling radiation response. A potential alternative to tissue-based methods of response prediction is analysis of the low molecular weight region of the serum proteome using surface-enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS). This technique is based on the premise that blood becomes endowed with an archive of protein-based histologic information as it circulates through the body.25 This is thought to represent byproducts of cellular metabolism such as cell-cell signaling molecules and species shed from dead or dying cells.26 SELDI-TOF-MS can detect multiple proteins and peptides in biologic samples based upon their time of flight down a vacuum chamber.27 Using data mining software, profiles of multiple protein patterns may be compared between test and control groups. The most common clinical example of this is the generation of specific proteomic patterns that allow discrimination of serum taken from patients with cancer or from healthy controls. In this role, it has been found to be capable of correctly identifying between groups with high sensitivity and specificity, being validated in many cancer subtypes including colorectal, lung, ovarian and breast cancer.28–31 Currently, SELDI-TOF-MS remains unassessed in the role of predicting response to radiation-based therapies. It may be ideally suited to this purpose as in contrast to tissue-based methods, it is minimally invasive and may be repeated at multiple time points through treatment. We report, herein, an investigation of SELDI-TOF-MS analysis of serum to predict and monitor tumor response in patients undergoing a standard multimodal protocol for rectal cancer.

Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed to gain further insight into this by assessing a cohort of Fabry patients using CMR.Fifty genotype-positive Fabry subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls (age 40±2 years; 59% male) were recruited. Patients had a mean Mainz severity score index of 15±2 (range 0-46), reflecting an overall mild degree of disease severity. Compared with controls, Fabry subjects had a 34% greater left ventricular mass (LVM) index (82±5 vs 61±2 g/m(2), p=0.001) and had a significantly greater papillary muscle contribution to total LVM (13±1 vs 6±0.5%, p0.001), even in the absence of left ventricular hypertrophy (LVH). Late gadolinium enhancement (LGE) was present in 15 Fabry subjects (9/21 males and 6/23 females). The most common site for LGE was the basal inferolateral wall (93%, 14/15). There was a positive association between LVM index and LGE. Despite this, there were two males and three females with no LVH that displayed LGE. Of Fabry subjects who were not on enzyme replacement therapy at enrolment (n=28), six were reclassified as having cardiac involvement (four LVH-negative/LGE-positive, one LVH-positive/LGE-positive and one LVH-positive/LGE-negative).CMR was able to detect cardiac involvement in 48% of this Fabry cohort, despite the overall mild disease phenotype of the cohort. Of those not on ERT, 21% were reclassified as having cardiac involvement allowing improved risk stratification and targeting of therapy.

Sphingolipid deposition in Fabry disease causes left ventricular (LV) hypertrophy, of which the accurate assessment is essential. Cardiovascular magnetic resonance (CMR) has been proposed as the gold standard. However, there is debate in the literature as to whether papillary muscles and trabeculations (P&T) should be included in LV mass (LVM). We examined the accuracy of 2 CMR methods of assessing LVM and LV volumes, including (M inc P&T) or excluding (M ex P&T) P&T, in a cohort of Fabry disease subjects (n = 20) compared to a matched control group (n = 20). Significant differences between the two measurement methods were observed for LV end-diastolic volume, LV end-systolic volume, LVM, and LV ejection fraction (LVEF) in both groups. These differences were significantly greater in the Fabry group compared to controls, except for LVEF. P&T contributed to a greater percentage of LVM in Fabry subjects than controls (20 ± 1% vs 13 ± 2%, p = 0.01). In the control group, both volume-derived methods (M inc P&T or MexP&T) provided accurate SV measurements compared with the internal reference of velocity-encoded aortic flow. In the Fabry group, inclusion of P&T (M inc P&T) resulted in good concordance with phase contrast flow imaging (difference between flow and volume techniques: 1 ± 3 ml, p = 0.7). The volumetric contribution of P&T in Fabry disease is markedly increased relative to healthy controls. Failure to account for this results in significant underestimation of LVM and results in misclassification of a proportion of subjects.

Sydney Translational Imaging Laboratory, Sydney Medical School and Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia Heart Research Institute, Sydney, NSW, Australia North Shore Heart Research Group, Kolling Institute, University of Sydney, Sydney, NSW, Australia Department of Radiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Sarcos Research Corporation, and the Center for Engineering Design at the University of Utah, have long been interested in both the fundamental and the applied aspects of robots and other computationally driven machines. We have produced substantial numbers of systems that function as products for commercial applications, and as advanced research tools specifically designed for experimental use. This paper reviews various aspects of the design and control of a number of robot-like machines ranging from our first projects, the Utah Arm and the Utah/MIT Dextrous Hand, to present work on humanoid robots and the Wearable Energetically Autonomous Robot (WEAR). Our systems have been used in: entertainment, operator remotization from hazardous environments, R&D, and medicine. In addition to the robots and their subsystems, extensive work has been devoted to command systems that drive the robots. Command systems have been: playback supervisors, teleoperation masters, and various higher level approaches based on work from the AI community. Playback interfaces have included motion capture mechanisms that provide movement-stream information to storage systems configured for later, repeated and coordinated, operation of many robots and associated mechanisms. Play-back command systems use human commands, from an “earlier” time, to command motions that are played out, over and over, mindlessly. Teleoperation “masters”, that operate in real-time with the robot, have ranged from simple motion capture devices, to more complex force reflective exoskeletal masters. Teleoperation interfaces have been composed of complex kinematic structures designed to perform motions compatible with operator movements and are attached via appropriate soft tissue interfaces. The masters emit lower level commands (joint angles) in real-time using the natural intelligence and sensory systems of the operator. AI-based command sources, blend higher level (simple) commands, with system and existing environmental states, to make decisions for the management of the robot. As with the playback systems, AI-based systems are programmed earlier to perform later operations. In the AI case, however, adaptive intelligence and sensory capabilities reside in the robot. Our general design approach has been to begin with the definition of desired objective behaviors, rather than the use of available components with their predefined technical specifications. With the technical specifications of the components necessary to achieve the desired behaviors defined, the components are either acquired, or in most cases, developed and built. The control system, which includes the operation of feedback approaches, acting in collaboration with physical machinery, is then defined and implemented. Control is considered a function of both feedback, and the designed-in performance of the robot’s physical machinery. It has not been true that bad performance from physical machine elements can be simply compensated out via innovative control methods and faster computers. After the completion of many projects we believe that the final frontier(s) of robotics reside at both ends of the brain and brawn spectrum. Both frontiers (barriers) are related to autonomy—intelligence/computation and energy/power. Recently, energetic autonomy has become a major interest at Sarcos and projects are underway to develop appropriate fuel-based servo-actuators to satisfy that need. Our objective is to develop power systems that are capable producing high performance servo-quality actuation for extended operating times without reenergizing the system. At the other end of the spectrum, we are working in collaboration with various groups to supply physical robots capable of operation under the control of advanced AI-based systems.

There is currently no reliable means to restage rectal cancers after neoadjuvant chemoradiation. Recent histological evidence shows that the epicentre for residual cancer cells is focussed directly underneath any residual mucosal abnormality (RMA). This proof-of-concept study aimed to determine the utility of a novel, minimally invasive method of incisional biopsy as a restaging tool. A secondary aim was to compare its performance to clinical response assessment.After surgical resection, 0.5 × 0.5 cm, full-thickness incisional biopsy was performed in 15 rectal cancers. Of these, 13 had RMA and 2 had mucosal cCR but a palpable intramural abnormality. In all patients, a full-thickness incisional biopsy was taken through the centre of these areas. The ypT stage of the incisional biopsy and the final total specimen were compared. Complete mucosal clinical response was deemed to have occurred when either no residual tumour or only a flat mucosal scar remained.Incisional biopsy correctly identified all patients that had been downstaged to ypT0; however, it also falsely identified 5 of 10 patients (50%) with yp residual disease as ypT0. Overall performance of incisional biopsy to detect residual cancer was 50% sensitivity, 100 % specificity, 100% PPV, and 50% NPV with an accuracy of 66%. A complete mucosal clinical response occurred in only one of five patients downstaged to ypT0 (20% sensitive). It also occurred in one patient, which was ultimately staged as ypT3.This prospective data demonstrates that incisional biopsy is not suitable as a stand-alone method to restage rectal cancer after CRT. Alternate or complementary means of restaging are needed.

Background Quantification of myocardial “area at risk” ( AAR ) and myocardial infarction ( MI ) zone is critical for assessing novel therapies targeting myocardial ischemia–reperfusion ( IR ) injury. Current “gold‐standard” methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride ( TTC ), requiring manual slicing and analysis. We aimed to develop and validate a high‐resolution 3‐dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR . Methods and Results Forty‐eight hours after IR was induced, rats were anesthetized and gadopentetate dimeglumine was administered intravenously. After 10 minutes, the coronary artery was re‐ligated and a solution containing iron oxide microparticles and Evan's Blue was infused (for comparison). Hearts were harvested and transversally sectioned for TTC staining. Ex vivo MR images of slices were acquired on a 9.4‐T magnet. T2* data allowed visualization of AAR , with microparticle‐associated signal loss in perfused regions. T1 data demonstrated gadolinium retention in infarcted zones. Close correlation ( r =0.92 to 0.94; P MRI and Evan's Blue/ TTC measures for both AAR and MI was observed when the combined techniques were applied to the same heart slice. However, 3D MRI acquisition and analysis of whole heart reduced intra‐observer variability compared to assessment of isolated slices, and allowed automated segmentation and analysis, thus reducing interobserver variation. Anatomical resolution of 81 μm 3 was achieved (versus ≈2 mm with manual slicing). Conclusions This novel, yet simple, MRI technique allows precise assessment of infarct and AAR zones. It removes the need for tissue slicing and provides opportunity for 3D digital analysis at high anatomical resolution in a streamlined manner accessible for all laboratories already performing IR experiments.

Patient size is 1 determinant in selecting a mechanical circulatory support device. The current pulsatile ventricular assist devices (VADs) were designed primarily for average-sized adults. The flexibility of the Thoratec VAD, however, has encouraged physicians to use it in a significant number of intermediate-sized older children and adolescents.We conducted a retrospective study in 58 children and adolescents18 years (41 boys, 17 girls) who had been supported with the Thoratec VAD in 27 centers worldwide as of December 1999. Mean patient age was 13.8 years (range, 7 to 17 years), and mean patient weight and body surface area were 51.6 kg (range, 17 to 93 kg) and 1.5 m(2) (range, 0.7 to 2.1 m(2)), respectively.Thirty-five patients (60%) survived to transplantation and 6 (10%) to recovery of the native heart, respectively; 38 were discharged from the hospital (66%). In the transplanted group, post-transplantation survival was 97%. Patient age and size were not associated with significantly increased risk for death or adverse events. Fifteen patients (27%) had 18 neurologic events during support, and 6 of these were fatal. Left atrial cannulation proved a risk factor for neurologic complications.The Thoratec VAD has successfully been used in a large number of children and adolescents with similar morbidity and mortality results as with adults. The risk of neurologic complications may be increased, particularly in patients cannulated in the left atria.

To evaluate the accuracy of thin-section computed tomography (CT) with expiratory scans in diagnosing early bronchiolitis obliterans after lung transplantation.Thin-section CT scans were reviewed by two observers blinded to the diagnoses in seven consecutive lung transplant recipients with histopathologically proved bronchiolitis obliterans (group A) and 21 with normal biopsy findings (group B). All patients had normal biopsy and stable pulmonary function test (PFT) results 2-36 weeks prior to CT. Patients with normal biopsy results were placed into subgroups based on abnormal (group B1) or stable (group B2) PFT results. Air-trapping extent on expiratory scans was scored on a 24-point scale.The mean air-trapping score in group A (6.6) was not significantly different from that in group B (4.5, P =. 17). The air-trapping score was significantly higher in groups A and B1 than in group B2 (6.2 and 2.6, respectively; P =.03). The frequency of an air-trapping score of 3 or more in groups A and B1 was significantly higher than that in group B2 (P =.03). By using a score of 3 or more to indicate air trapping, the sensitivity of expiratory CT was 74%, specificity was 67%, and accuracy was 71%.Thin-section CT, including expiratory scans, is of limited accuracy in diagnosing early bronchiolitis obliterans after lung transplantation.

Background: Bronchiolitis obliterans occurs in 30% to 80% of lung-transplant recipients and is a direct cause of death in more than 40% of patients with this complication. This study assessed the potential utility of measuring fibroblast-proliferative activity in bronchoalveolar lavage fluid from lung-transplant recipients to better understand the pathogenesis of this process. Methods The capacity of bronchoalveolar lavage fluid obtained from transplant recipients, during routine surveillance bronchoscopy, to stimulate the proliferation of human lung fibroblasts in vitro was assessed retrospectively and compared to that of control subjects. For each recipient, a correlation was made between the fibroblast-proliferative activity in serial lavage samples over time and the other modalities employed for detecting post-transplant complications including spirometry, transbronchial lung biopsy, and high-resolution computed tomography. Results There was a significant difference in fibroblast-proliferative activity between volunteer and transplant recipient groups ( p = 0.002). Further, for each transplant recipient, the decline in the forced expired flow rate between 25% and 75% of expired volume (FEF 25%–75% ) was correlated with the mean fibroblast-proliferative activity during the period of this study ( r = 0.83; p = 0.04). Conclusions A sustained increase in fibroblast-proliferative activity in lavage supernatant precedes both histologic and physiologic evidence of bronchiolitis obliterans. Relative to an increase in fibroblast-proliferative activity or abnormalities in FEF 25%–75% , a decrease in forced expiratory volume in 1 second is a late finding.

Thoracic aortic aneurysm (TAA) is reported with an occurrence of 4.5–5.9/100,000 persons per year (Davis et al. 2014). Physiopathology of TAA includes modification of tissue influenced by flow modi...