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“Repent you, fair one, of the sin you carry?” – “I do; and bear the shame most patiently”. Thus begins one of the most overlooked dialogues in Measure for Measure. Hidden in what appears to be an i...

For investigating the potential for personalized treatment of pancreatic cancer, two- and three-photon autofluorescence and second and third harmonic generation images were simultaneously generated from in vivo pancreatic tumor patient-derived xenograft (PDX) mice. Two different treatment regimens were administered to PDX mice for 5 weeks and compared. Control mice were treated only with saline. Mice were classified into three groups according to their response to the treatment: responsive, resistant, and control. Optical redox ratios were calculated from tumor regions which showed differences between the responsive group compared to the resistant and control groups.

ObjectivesWe undertook a rapid systematic review with the aim of identifying evidence that could be used to answer the following research questions: (1) What is the clinical effectiveness of tests that detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform COVID-19 diagnosis? (2) What is the clinical effectiveness of tests that detect the presence of antibodies to the SARS-CoV-2 virus to inform COVID-19 diagnosis?Design and settingSystematic review and meta-analysis of studies of diagnostic test accuracy. We systematically searched for all published evidence on the effectiveness of tests for the presence of SARS-CoV-2 virus, or antibodies to SARS-CoV-2, up to 4 May 2020, and assessed relevant studies for risks of bias using the QUADAS-2 framework.Main outcome measuresMeasures of diagnostic accuracy (sensitivity, specificity, positive/negative predictive value) were the main outcomes of interest. We also included studies that reported influence of testing on subsequent patient management, and that reported virus/antibody detection rates where these facilitated comparisons of testing in different settings, different populations or using different sampling methods.Results38 studies on SARS-CoV-2 virus testing and 25 studies on SARS-CoV-2 antibody testing were identified. We identified high or unclear risks of bias in the majority of studies, most commonly as a result of unclear methods of patient selection and test conduct, or because of the use of a reference standard that may not definitively diagnose COVID-19. The majority were in hospital settings, in patients with confirmed or suspected COVID-19 infection. Pooled analysis of 16 studies (3818 patients) estimated a sensitivity of 87.8% (95% CI 81.5% to 92.2%) for an initial reverse-transcriptase PCR test. For antibody tests, 10 studies reported diagnostic accuracy outcomes: sensitivity ranged from 18.4% to 96.1% and specificity 88.9% to 100%. However, the lack of a true reference standard for SARS-CoV-2 diagnosis makes it challenging to assess the true diagnostic accuracy of these tests. Eighteen studies reporting different sampling methods suggest that for virus tests, the type of sample obtained/type of tissue sampled could influence test accuracy. Finally, we searched for, but did not identify, any evidence on how any test influences subsequent patient management.ConclusionsEvidence is rapidly emerging on the effectiveness of tests for COVID-19 diagnosis and management, but important uncertainties about their effectiveness and most appropriate application remain. Estimates of diagnostic accuracy should be interpreted bearing in mind the absence of a definitive reference standard to diagnose or rule out COVID-19 infection. More evidence is needed about the effectiveness of testing outside of hospital settings and in mild or asymptomatic cases. Implementation of public health strategies centred on COVID-19 testing provides opportunities to explore these important areas of research.

STRUCTURED ABSTRACTObjectivesWe undertook a rapid systematic review with the aim of identifying evidence that could be used to answer the following research questions: (1) What is the clinical effectiveness of tests that detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform COVID-19 diagnosis? (2) What is the clinical effectiveness of tests that detect the presence of antibodies to the SARS-CoV-2 virus to inform COVID-19 diagnosis?Designsystematic review and meta-analysis of studies of diagnostic test accuracy. We systematically searched for all published evidence on the effectiveness of tests for the presence of SARS-Cov-2 virus, or antibodies to SARS-CoV-2, up to 4 May 2020, and assessed relevant studies for risks of bias using the QUADAS-2 framework.Main outcome measuresmeasures of diagnostic accuracy (sensitivity, specificity, positive/negative predictive value) were the main outcomes of interest. We also included studies that reported influence of testing on subsequent patient management, and that reported virus/antibody detection rates where these facilitated comparisons of testing in different settings, different populations, or using different sampling methods.Results38 studies on SARS-CoV-2 virus testing and 25 studies on SARS-CoV-2 antibody testing were identified. We identified high or unclear risks of bias in the majority of studies, most commonly as a result of unclear methods of patient selection and test conduct, or because of the use of a reference standard that may not definitively diagnose COVID-19. The majority were in hospital settings, in patients with confirmed or suspected COVID-19 infection. Pooled analysis of 16 studies (3818 patients) estimated a sensitivity of 87.8% (95% confidence interval 81.5% to 92.2%) for an initial reverse-transcriptase polymerase chain reaction test. For antibody tests, ten studies reported diagnostic accuracy outcomes: sensitivity ranged from 18.4% to 96.1% and specificity 88.9% to 100%. However, the lack of a true reference standard for SARS-CoV-2 diagnosis makes it challenging to assess the true diagnostic accuracy of these tests. Eighteen studies reporting different sampling methods suggest that for virus tests, the type of sample obtained/type of tissue sampled could influence test accuracy. Finally we searched for, but did not identify, any evidence on how any test influences subsequent patient management.ConclusionsEvidence is rapidly emerging on the effectiveness of tests for COVID-19 diagnosis and management, but important uncertainties about their effectiveness and most appropriate application remain. Estimates of diagnostic accuracy should be interpreted bearing in mind the absence of a definitive reference standard to diagnose or rule out COVID-19 infection. More evidence is needed about the effectiveness of testing outside of hospital settings and in mild or asymptomatic cases. Implementation of public health strategies centred on COVID-19 testing provides opportunities to explore these important areas of research.SUMMARY BOXWhat is already known about this subject?Tests for the presence of the SARS-CoV-2 virus, and antibodies to the virus, are being deployed rapidly and at scale as part of the global response to COVID-19.At the outset of this work (March 2020), no high-quality evidence reviews on the effectiveness of SARS-CoV-2 virus or antibody tests were available.High-quality evidence reviews are required to help decision makers deploy and interpret these tests effectively.What are the new findings?Here, we synthesise evidence on the diagnostic accuracy of all known tests for SARS-CoV-2, as well as tests for antibodies to SARS-CoV-2.We also systematically summarise evidence on the influence of tissue sample site on virus test detection rates, and the influence of test timing relative to disease course on antibody detection. The results suggest that both these factors could influence test results.We conclude that evidence on SARS-CoV-2 virus and antibody tests is nascent and significant uncertainties remain in the evidence base regarding their clinical and public health application. We also note that potential risks of bias exist within many of the available studies.How might it impact on clinical practice in the foreseeable future?In a rapidly developing pandemic, the widespread use of testing is an essential element in the development of effective public health strategies, but it is important to acknowledge the gaps and limitations that exist in the current evidence base and that, where possible, these should be addressed in future studies.In particular, more evidence is needed on the performance of point-of-care or near-patient tests compared to their laboratory equivalents, and results of testing in people with no or minimal symptoms in community-based settings needs further analysis.

Aim The aim of this study was to explore the value of the FRANCE-2 score in associating with clinical outcome in the medium and short-term after TAVI and to compare its relative merits with other risk score models. Methods 187 consecutive patients undergoing TAVI in a single UK centre were retrospectively studied. The FRANCE-2, logistic EuroSCORE, EuroSCORE II, German AV and STS/ACC TVT risk scores were calculated retrospectively and c-statistics associating with mortality were applied. Survival outcomes were compared between different risk groups according to the FRANCE-2 scores. Results Of the 187 patients, 57.2% were male and their mean age was 80.9 ± 6.9 years. The c-index of FRANCE-2 score for predicting 30-day mortality was 0.793 (p = 0.009), for 1-year mortality 0.679 (p = 0.016) and for 2-year mortality was 0.613 (p = 0.088). The mean survival time for patients with a high FRANCE-2 score (18.6 months) was significantly less than for patients with low and moderate scores (p = 0.0004). The logistic EuroSCORE and EuroSCORE II were poorly associated with 30-day and 1-year mortality. STS/ACC TVT score was best predictive of 1-year mortality and German AV score was moderately predictive of 30-day mortality. Conclusions The FRANCE-2 risk score is associated with differential short- and medium-term survival in patients undergoing TAVI. The presence of a high FRANCE-2 score (>5) is associated with poor survival. The FRANCE-2 scoring system could be considered as a useful additional tool by the Heart multidisciplinary team (MDT) in identifying patients who are likely to have limited survival benefit although this requires further prospective evaluation.

A series of placebo-controlled trials were conducted in horses, cattle and goats in different seasons and bioclimatic regions of New South Wales and Queensland, Australia, to evaluate the ability of BioWorma®, a feed supplement containing the spores of Duddingtonia flagrans IAH 1297, to reduce the larval development of parasitic gastrointestinal nematodes (GIN) and their subsequent migration from faeces onto the surrounding pasture. In each trial, faeces were collected from animals harbouring a burden of nematode parasites following a period of supplementation with a placebo and again after supplementation with BioWorma. The faeces were manually placed onto pasture plots at one or two distinct geographical sites and the effect of treatment was determined by subsequent monitoring the numbers of parasitic larvae on the pasture surrounding the faecal pats at two weekly intervals over an eight week period. The results for these studies showed that administration of BioWorma at a minimum daily dose of 3 × 104 spores/kg bodyweight reduced parasite larvae in the pasture surrounding the faeces by 53–99 % over an eight week post treatment period in horses, cattle and goats in a range of bioclimatic zones and in different seasons. Overall, the studies with BioWorma show substantial reductions in GIN infectivity of pasture surrounding faeces of treated horses, cattle and goats (P

Simultaneous label-free autofluorescence multi-harmonic (SLAM) microscopy images of treated and non-treated mice with xenografts derived from human pancreatic tumors were acquired and analyzed for evaluation of chemotherapeutic drug response.

Introduction There is a high prevalence of patent foramen ovale (PFO) in patients with cryptogenic stroke; paradoxical embolism may be implicated in some but not all of these. Percutaneous device PFO closure reduces the risk of recurrent emboli but the success of this treatment is dependent on appropriate patient selection. The work-up of patients with cryptogenic stroke and PFO is best undertaken by a multi-disciplinary team (MDT). Aim The aim was to evaluate the impact of a methodical approach to MDT investigation and work-up of patients with cryptogenic stroke and PFO on the final diagnosis and selection of patients for device PFO closure in a UK centre. Methods The study was done in a single tertiary cardiac centre providing a PFO device closure service to a population of 1.3 million. Consecutive patients referred to the service between March 2011 and January 2017 were studied. Assessment included clinical consultation and expert review of all cardiac imaging (TOE and bubble contrast TTE), brain imaging (CT, DWI MRI, CT angiography), thrombophilia and arrhythmia investigations. Information about the MDT conclusions was obtained from meeting minutes, electronic and paper patient records. Results 171 patients [51% female, mean age of 42 years (SD: ±16)] were assessed. The median number of MDT discussions was 1 per patient (range 1–5). Referral was with a cerebral infarct in 82%, transient cerebral ischaemia in 12% and peripheral emboli in 6%. Brain imaging confirmed the presence of cerebral infarction in 74% of patients. Cardiac imaging confirmed the presence of a PFO in 88%, an ASD in 5% and both in 4%; the intra-atrial septum was intact in 3%. One ‘high risk’ echo marker for paradoxical embolism was present in 44% of patients; an atrial septal aneurysm (23%), large right-to-left shunt (20%) or spontaneous shunt (43%). Clinically significant atrial arrhythmia was detected in 5% and thrombophilia testing was abnormal in 5% with lupus anticoagulant being positive in 62% of this subgroup. The final diagnoses are summarized in the figure 1. Paradoxical embolism was proposed if there was cerebral infarction typical of thrombo-embolism in the absence of vascular disease or arrhythmia and in the presence of PFO or ASD with a ’high-risk’ ECHO marker. Based on these criteria, device closure was recommended in 41% of patients. The remainder received treatment appropriate to their diagnosis: antiplatelet therapy in 36%, anti-coagulants in 10% and no treatment in 15%. Conclusion In patients with cryptogenic stroke who have a PFO, paradoxical embolism is implicated in the minority. Methodical work-up of patients by an MDT results in a range of diagnoses most of which are unrelated to the PFO. While clinical follow-up is required in all patients included in this study, we conclude that PFO device closure should be offered cautiously and only after careful multi-disciplinary assessment. Conflict of Interest None to declare

Objectives The authors present the UK and Irish real-world learning curve experience of the Evolut R transcatheter heart valve. Background The Evolut R is a self-expanding, repositionable, and fully recapturable second-generation transcatheter heart valve with several novel design features to improve outcomes and reduce complications. Methods Clinical, procedural, and 30-day outcome data were prospectively collected for the first 264 patients to receive the Evolut R valve in the United Kingdom and Ireland. Results A total of 264 consecutive Evolut R implantations were performed across 9 centers. The mean age was 81.1 ± 7.8 years, and the mean logistic European System for Cardiac Operative Risk Evaluation score was 19.9 ± 13.7%. Procedural indications included aortic stenosis (72.0%), mixed aortic valve disease (17.4%), and failing aortic valve bioprostheses (10.6%). Conscious sedation was used in 39.8% of patients and transfemoral access in 93.6%. The procedural success rate was 91.3%, and paravalvular leak immediately after implantation was mild or less in 92.3%. Major complications were rare: cardiac tamponade in 0.4%, conversion to sternotomy in 0.8%, annular rupture in 0.0%, coronary occlusion in 0.8%, major vascular in 5.3%, acute kidney injury in 6.1%, new permanent pacemaker implantation in 14.7%, and procedure-related death in 0.0%. At 30-day follow-up, survival was 97.7%, paravalvular leak was mild or less in 92.3%, and the stroke rate was 3.8%. Conclusions This registry represents the largest published real-world experience of the Evolut R valve. The procedural success rate was high and safety was excellent, comparable with previous studies of the Evolut R valve and other second-generation devices. The low rate of complications represents an improvement on first-generation devices.

Transcatheter aortic valve implantation (TAVI) for severe, symptomatic aortic stenosis improves quality of life and survival in most patients. It is, however, important to identify patients who are unlikely to get these benefits from TAVI so that futile treatment can be avoided. Futility in this

Diseases in intensive poultry flocks may occur due to viral, bacterial, fungal, protozoal, metazoan or arthropod infections or infestations. This chapter describes disease preventative measures, health monitoring and disease investigation techniques, and the management of sick meat chicken flocks. This chapter covers dealing with the emergency of an outbreak of disease in the flock, including hygiene procedures and methods of disposing of dead birds. The chapter examines the challenges inherent in poultry disease control and looks forward to future trends in this area.

While hyperspectral data are very rich in information, processing the hyperspectral data poses several challenges regarding computational requirements, information redundancy removal, relevant information identification, and modeling accuracy. In this paper we present a new methodology for combining unsupervised and supervised methods under classification accuracy and computational requirement constraints that is designed to perform hyperspectral band (wavelength range) selection and statistical modeling method selection. The band and method selections are utilized for prediction of continuous ground variables using airborne hyperspectral measurements. The novelty of the proposed work is in combining strengths of unsupervised and supervised band selection methods to build a computationally efficient and accurate band selection system. The unsupervised methods are used to rank hyperspectral bands while the accuracy of the predictions of supervised methods are used to score those rankings. We conducted experiments with seven unsupervised and three supervised methods. The list of unsupervised methods includes information entropy, first and second spectral derivative, spatial contrast, spectral ratio, correlation, and principal component analysis ranking combined with regression, regression tree, and instance-based supervised methods. These methods were applied to a data set that relates ground measurements of soil electrical conductivity with airborne hyperspectral image values. The outcomes of our analysis led to a conclusion that the optimum number of bands in this domain is the top four to eight bands obtained by the entropy unsupervised method followed by the regression tree supervised method evaluation. Although the proposed band selection approach is demonstrated with a data set from the precision agriculture domain, it applies in other hyperspectral application domains.

Hyperspectral remote sensing produces large volumes of data, quite often requiring hundreds of megabytes to gigabytes of memory storage for a small geographical area for one-time data collection. Although the high spectral resolution of hyperspectral data is quite useful for capturing and discriminating subtle differences in geospatial characteristics of the target, it contains redundant information at the band level. The objective of this study was to identify those bands that contain the most information needed for characterizing a specific geospatial feature with minimal redundancy. Band selection is performed with both unsupervised and supervised approaches. Five methods (three unsupervised and two supervised) are proposed and compared to identify hyperspectral image bands to characterize soil electrical conductivity and canopy coverage in agricultural fields. The unsupervised approach includes information entropy measure and first and second derivatives along the spectral axis. The supervised approach selects hyperspectral bands based on supplemental ground truth data using principal component analysis (PCA) and artificial neural network (ANN) based models. Each hyperspectral image band was ranked using all five methods. Twenty best bands were selected by each method with the focus on soil and plant canopy characterization in precision agriculture. The results showed that each of these methods may be appropriate for different applications. The entropy measure and PCA were quite useful for selecting bands with the most information content, while derivative methods could be used for identifying absorption features. ANN measure was the most useful in selecting bands specific to a target characteristic with minimum information redundancy. The results also indicated that a combination of wavebands with different bandwidths will allow use of fewer than 20 bands used in this study to represent the information contained in the top 20 bands, thus reducing image data dimensionality and volume considerably.

In 1994 the archive of Liddon House, London, was moved to Pusey House in Oxford. The journals of Henry Parry Liddon, kept more or less daily from 1858 to 1890 (the year of Liddon's death), thus came to be housed alongside the enormous correspondence of Edward Bouverie Pusey which Liddon himself spent much effort in collecting. Liddon's journal entries from 1863 onwards contain a number of references to the young Gerard Manley Hopkins, then an undergraduate at Balliol. A number of Hopkins scholars have made use of the journals in their research but none, to my knowledge, has examined them since their move to Oxford. Recently, a number of other documents have come to light which relate to Hopkins's time in Oxford, and in particular to his conversion. One of these documents strongly suggests that the only extant letter from Edward Pusey to Hopkins has been misdated since its publication in 1935, and hence that the accepted chronology of the days leading up to Hopkins's reception into the Roman Catholic Church needs slightly to be revised.

Valve surgery remains the treatment of choice for most significant valve lesions. Symptomatic improvement has been well demonstrated in a number of studies and is usually sustained into the late postoperative period, especially when valve replacement is undertaken for stenotic lesions. Invasive studies have shown that symptomatic relief is consistently accompanied by haemodynamic improvement, and the overall superiority of surgical intervention over conservative medical treatment for most patients with advanced valve disease has been firmly established. The analysis of survival rates of patients following valve replacement relative to age and sex matched populations have shown an impaired prognosis in all but a minority.1 In patients older than 65 years undergoing aortic valve replacement for aortic stenosis, relative survival is “normalised” after the first postoperative year, but in all other indications an excess late mortality has been observed in surgical patients. Long term follow up studies consistently report better survival rates in patients undergoing aortic rather than mitral valve replacement, with 10 year actuarial survival rates of approximately 65% for aortic valve replacement, 55% for mitral valve replacement, and 55% for double (aortic and mitral) valve replacement. Late mortality is greater when surgery is undertaken for regurgitant as opposed to stenotic lesions, while long term survival is better in the context of degenerative as opposed to ischaemic or rheumatic valve pathologies. These observations illustrate the fact that long term mortality following valve replacement is most reflective of the nature of the original disease process, the pre- and postoperative state of the myocardium and coronary circulation, as well as the general wellbeing of the patient with valve related deaths being relatively infrequent. Approximately 60% of late mortality is attributable to cardiac causes that are independent of the valve surgery (namely, cardiac failure, myocardial infarction, arrhythmia or sudden death), approximately 20% is …