On the Rozansky-Witten weight systems

Ideas of Rozansky and Witten, as developed by Kapranov, show that a complex symplectic manifold X gives rise to Vassiliev weight systems. In this paper we study these weight systems by using D(X), the derived category of coherent sheaves on X. The main idea (stated here a little imprecisely) is that D(X) is the category of modules over the shifted tangent sheaf, which is a Lie algebra object in D(X); the weight systems then arise from this Lie algebra in a standard way. The other main results are a description of the symmetric algebra, universal enveloping algebra, and Duflo isomorphism in this context, and the fact that a slight modification of D(X) has the structure of a braided ribbon category, which gives another way to look at the associated invariants of links. Our original motivation for this work was to try to gain insight into the Jacobi diagram algebras used in Vassiliev theory by looking at them in a new light, but there are other potential applications, in particular to the rigorous construction of the (1+1+1)-dimensional Rozansky-Witten TQFT, and to hyperkaehler geometry

Rapid metagenomics for diagnosis of bloodstream and respiratory tract nosocomial infections: current status and future prospects

Introduction: Nosocomial infections represent a major problem for the health-care systems worldwide. Currently, diagnosis relies on microbiological culture, which is slow and has poor sensitivity. While waiting for a diagnosis, patients are treated with empiric broad spectrum antimicrobials, which are often inappropriate for the infecting pathogen. This results in poor patient outcomes, poor antimicrobial stewardship and increased costs for health-care systems. Areas covered: Clinical metagenomics (CMg), the application of metagenomic sequencing for the diagnosis of infection, has the potential to become a viable alternative to culture that can offer rapid results with high accuracy. In this article, we review current CMg methods for the diagnosis of nosocomial bloodstream (BSI) and lower respiratory-tract infections (LRTI). Expert opinion: CMg approaches are more accurate in LRTI compared to BSI. This is because BSIs are caused by low pathogen numbers in a high background of human cells. To overcome this, most approaches focus on cell-free DNA, but, to date, these tests are not accurate enough yet to replace blood culture. The higher pathogen numbers in LRTI samples make this a more suitable for CMg and accurate approaches have been developed, which are likely to be implemented in hospitals within the next 2–5 years

Ideology, Grandstanding, and Strategic Party Disloyalty in British Parliament

Strong party discipline is a core feature of Westminster parliamentary systems. Parties typically compel Members of Parliament (MPs) to support the party position regardless of MPs' individual preferences. Rebellion, however, does occur. Using an original dataset of MP votes and speeches in the British House of Commons from 1992 to 2015, coupled with new estimations of MPs' ideological positions within their party, we find evidence that MPs use rebellion to strategically differentiate themselves from their party. The strategy that MPs employ is contingent upon an interaction of ideological extremity with party control of government. Extremists are loyal when their party is in the opposition, but these same extremists become more likely to rebel when their party controls government. Additionally, they emphasize their rebellion through speeches. Existing models of rebellion and party discipline do not account for government agenda control and do not explain these patterns

Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients

A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre. In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706-25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected. A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study

Preliminary evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection

Aims This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required

An optimised protocol for detection of SARS-CoV-2 in stool

Background SARS-CoV-2 has been detected in stool samples of COVID-19 patients, with potential implications for faecal-oral transmission. Compared to nasopharyngeal swab samples, the complexity of the stool matrix poses a challenge in the detection of the virus that has not yet been solved. However, robust and reliable methods are needed to estimate the prevalence and persistence of SARS-CoV-2 in the gut and to ensure the safety of microbiome-based procedures such as faecal microbiota transplant (FMT). The aim of this study was to establish a sensitive and reliable method for detecting SARS-CoV-2 in stool samples. Results Stool samples from individuals free of SARS-CoV-2 were homogenised in saline buffer and spiked with a known titre of inactivated virus ranging from 50 to 750 viral particles per 100 mg stool. Viral particles were concentrated by ultrafiltration, RNA was extracted, and SARS-CoV-2 was detected via real-time reverse-transcription polymerase chain reaction (RT-qPCR) using the CDC primers and probes. The RNA extraction procedure we used allowed for the detection of SARS-CoV-2 via RT-qPCR in most of the stool samples tested. We could detect as few as 50 viral particles per 100 mg of stool. However, high variability was observed across samples at low viral titres. The primer set targeting the N1 region provided more reliable and precise results and for this primer set our method had a limit of detection of 1 viral particle per mg of stool. Conclusions Here we describe a sensitive method for detecting SARS-CoV-2 in stool samples. This method can be used to establish the persistence of SARS-CoV-2 in stool and ensure the safety of clinical practices such as FMT. </jats:sec

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics

Tuberculosis Trends in Saudis and Non-Saudis in the Kingdom of Saudi Arabia – A 10 Year Retrospective Study (2000–2009)

Tuberculosis (TB) remains a public health problem in the Kingdom of Saudi Arabia (KSA), which has a very large labour force from high TB endemic countries. Understanding the epidemiological and clinical features of the TB problem, and the TB burden in the immigrant workforce, is necessary for improved planning and implementation of TB services and prevention measures