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The soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a biomarker for the risk stratification of patients presenting with acute infections. However, most studies evaluating suPAR have used platform-based assays, the diagnostic accuracy of which may differ from point-of-care tests capable of informing timely patient triage in settings without established laboratory capacity.Using samples and data collected during a prospective cohort study of 425 patients presenting with moderate Covid-19 to two hospitals in India, we evaluated the analytical performance and diagnostic accuracy of a commercially-available rapid diagnostic test (RDT) for suPAR, using an enzyme-linked immunoassay (ELISA) as the reference standard. Although agreement between the two tests was limited (bias = −2.46 ng/mL [95% CI = −2.65 to −2.27 ng/mL]), diagnostic accuracy to predict progression to supplemental oxygen requirement was comparable, whether suPAR was used alone (area under the receiver operating characteristic curve [AUC] of RDT = 0.73 [95% CI = 0.68 to 0.79] vs. AUC of ELISA = 0.70 [95% CI = 0.63 to 0.76]; p = 0.12) or as part of a previously published multivariable clinical prediction model (AUC of RDT-based model = 0.74 [95% CI = 0.66 to 0.83] vs. AUC of ELISA-based model = 0.72 [95% CI = 0.64 to 0.81]; p = 0.78).Lack of agreement between the suPAR RDT and ELISA in our cohort warrants further investigation and highlights the importance of assessing candidate point-of-care tests to ensure management algorithms reflect the assay that will ultimately be used to inform patient care. The availability of a quantitative point-of-care test for suPAR opens the door to suPAR-guided risk stratification of patients with Covid-19 and other acute infections in settings with limited laboratory capacity.

BackgroundSevere febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens.MethodA pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated.ResultsThe expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidalSalmonella,Plasmodiumspecies andMycobacterium tuberculosisas the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients.ConclusionThis work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.

Background In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. Methods We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 30 BPM; SpO2/FiO2 Results In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72–0.74) and calibration (calibration slopes: 1.01–1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. Conclusions We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

As liaison librarians embedded in the faculties and disciplines of the University of Adelaide, Learning and Research Services staff are working to significant changes in educational philosophies and practices. In 2016, we formed a Learning and Teaching Community of Practice (CoP), designed to ground our teaching of research skills and digital literacies in current pedagogy and new teaching methodologies. Our CoP was aligned with the university's commitment to 'Small Group Discovery Experience’ teaching enhanced by the 'flipped classroom' model and new educational technologies. This article examines the benefits and opportunities created by our community of practice and considers options for future development.

Background In 2012, the World Health Organization (WHO) estimated 78 million cases of Neisseria gonorrhoea (NG) worldwide and recent reports indicate an increase in NG resistance to current antibiotic therapies globally. Chlamydia trachomatis (CT) infection is more prevalent than NG and current syndromic management guidelines are designed to simultaneously treat both bacteria with a combination of antibiotics to avoid missing treatment. In resource constrained settings many patients with urethral or vaginal discharge presenting at primary healthcare settings (PHC) are overtreated due to syndromic management, which lacks appropriate diagnostic tools for CT and NG differentiation in these settings. Methods To address this gap, the Foundation for Innovative New Diagnostics (FIND) and WHO collaborated on the development of Target Product Profiles (TPPs) to guide the development of appropriate diagnostics tools for improved clinical management of NG and CT infections. Using a Delphi-like process involving two serial surveys to solicit input from over 52 experts. Results Two TPPs for the appropriate identification of NG (and NG/CT) and its susceptibility/resistance profile to antibiotics were developed and will be publicly available on the WHO and FIND websites. A request for proposals is in process to stimulate the development of diagnostic tools that meet the technical characteristics of these TPPs. Conclusion TPPs for rapid identification of NG-positive patients at PHC and for identification of NG susceptibility/resistance to antibiotics are urgently needed. Technology advancements over the past years may enable development of improved tests to support uptake and wide scale use in PHC. A reflex antibiotic susceptibility test would be useful to further guide prescription of current therapies. Results of this work will guide the development of new and appropriate diagnostics in the next 3–5 years, to enable improved patient management and conservation of new antibiotics that will become available. Disclosure No significant relationships.

Bacterial blood stream infections (BSI) are a common cause of mortality and morbidity globally. As the causative agents and the resulting treatment decisions vary, near-patient testing and surveillance tools are necessary to monitor bacterial causes and resistance to antimicrobial agents. The gold standard to identify BSIs is blood culture (BC), a methodology not widely available in resource-limited settings. The aim of the study was to map out a target product profile of a simplified BC system (SBCS) to inform product development efforts. To identify the desired characteristics of a SBCS, we enlisted a small group of specialists working in Africa and Asia. Questions were used to understand challenges and how these constraints inform system requirements. The specialists were infectious disease physicians, public health/clinical microbiologists, clinical researchers, and technology experts with different geographical backgrounds. All suggested that BC should ideally be available at the district hospital level. Many of the same operational challenges, such as limited availability of culture bottles, electricity and internet connectivity, profuse dust, the lack of ambient temperature control, and human capacity constraints were identified across the different regions. BCs, although the accepted gold standard for diagnosis of BSIs, are not widely available outside of reference/research centers in Africa and Asia. To extend the reach of this important tool, it is crucial to engage product developers and academic research partners to develop accessible alternatives.

BackgroundThere is a need for a rapid diagnostic point of care test to detect Neisseria gonorrhoeae (NG) infection to prevent incorrect, lack or excess of treatment resulting from current syndromic management in low-resource settings. An assay to identify NG antimicrobial resistance (AMR) is also highly desirable to facilitate antibiotic stewardship. Here we describe the development of two target product profiles (TPPs): one for a test for etiological diagnosis of NG and Chlamydia trachomatis (CT) (TPP1) and one for the detection of NG AMR/susceptibility (TPP2).MethodsDraft TPPs were initially developed based on a landscape analysis of existing diagnostics and expert input. TPPs were refined via an online Delphi survey with two rounds of input from 68 respondents. TPP characteristics on which ResultsThe need for a test to identify NG in patients with urethral or vaginal discharge was identified as a minimal requirement of TPP1, with a test that can diagnose NG in asymptomatic patients as the optimal requirement. A sensitivity of 80% was considered acceptable, either in context of syndromic management or screening high-risk populations. For TPP2, the agreed minimal requirement was for a test to be used at level 2 healthcare facilities and above, with an optimal requirement of level 1 or above. A lateral flow format was preferred for TPP1, while it was considered likely that TPP2 would require a molecular format. A total of 31 test characteristics were included in TPP1 and 27 in TPP2.ConclusionsFollowing the working group revisions, TPPs were posted online for public feedback for two months, and are now finalized. The final TPPs are currently guiding the development of new diagnostics that meet the defined characteristics to reach the market within two years.

Review Essay: The Watch Tower by Elizabeth Harrower

2012, the National Year of Reading (NYR), was celebrated in libraries, schools and community centres throughout Australia. At the University of Adelaide, we celebrated our academic culture of literary teaching and research with a range of programmes and initiatives based in the humanities faculty. The Barr Smith Library played an integral part in supporting the University's literary culture with our collections, services and expertise. This paper describes my role as an embedded librarian in the humanities, and the different areas of professional practice that I employed for NYR in 2012: collection development and promotion; teaching; collaboration with academic colleagues; the use of new educational technologies and social media. It provides an insight into some of the current trends and future opportunities that are shaping the role of the subject librarian in academic libraries.

Review of Harry Freedman, The Talmud: a biography

Review of The Road to Middlemarch by Rebecca Mead

The National Biodefense Analysis and Countermeasures Center (NBACC) plays a central role in the US Biodefense community, and its unique mission has driven NBACC to make dual use research of concern (DURC) review a focus since inception. Review of research results prior to external release began in 2007 and an institution-level review of all projects that considers DURC was implemented beginning in 2011. The DURC review process at NBACC has evolved through four approaches—each with advantages and disadvantages—that are all consistent with the recently issued U.S. Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern. The current NBACC review process emphasizes Principal Investigator (PI) ownership and accountability, builds transparency in DURC review, and is specifically tailored to NBACC in order to reinforce an institutional culture of responsibility. This paper summarizes NBACC’s evolutionary process for effective DURC review.

Introduction Accurate incidence estimates are needed to characterize the HIV epidemic and guide prevention efforts. HIV Incidence assays are cost-effective laboratory assays that provide incidence estimates from cross-sectional surveys. We conducted a global market assessment of HIV incidence assays under three market scenarios and estimated the economic value of improved incidence assays. Methods We interviewed 27 stakeholders, and reviewed journal articles, working group proceedings, and manufacturers’ sales figures. We determined HIV incidence assay use in 2014, and estimated use in 2015 to 2017 and in 5 to 10-years under three market scenarios, as well as the cost of conducting national and key population surveys using an HIV incidence assay with improved performance. Results Global 2014 HIV incidence assay use was 308,900 tests, highest in Asia and mostly for case- and population-based surveillance. Estimated 2015 to 2017 use was 94,475 annually, with declines due to China and the United States discontinuing incidence assay use for domestic surveillance. Annual projected 5 to 10 year use under scenario 1 – no change in technology – was 94,475. For scenario 2 – a moderately improved incidence assay – projected annual use was 286,031. Projected annual use for scenario 3 – game-changing technologies with an HIV incidence assay part of (a) standard confirmatory testing, and (b) standard rapid testing, were 500,000 and 180 million, respectively. As HIV incidence assay precision increases, decreased sample sizes required for incidence estimation resulted in $5 to 23 million annual reductions in survey costs and easily offset the approximately $3 million required to develop a new assay. Conclusions Improved HIV incidence assays could substantially reduce HIV incidence estimation costs. Continued development of HIV incidence assays with improved performance is required to realize these cost benefits.

Review of The Censor’s Library, by Nicole Moore

Review of How to be a Good Wife by Emma Chapman

Review of The Burning Library: Our Great Novelists Lost and Found by Geordie Williamson

Review of The Spying Game:An Australian Angle by Bruce Bennett

Review of Angela Carter and Decadence: Critical Fictions/Fictional Critiques by Maggie Tonkin

Review of 'Nine Lives' by Susan Sheridan

Review of 'The Generation of Edward Hyde' by Jay Bland.

Review of 'Journeys to the Interior' by Nicolas Rothwell.

Sequential treatment with chemotherapy and radioimmunotherapy (RIT) results in overall response rates > 90% in untreated follicular lymphoma (FL). We previously reported a complete response rate (CR) of 89% in 60 patients with stage II–IV symptomatic or bulky FL who received a short-course CHOP-Rituximab (R) x 3 cycles followed by Ibritumomab Tiuxetan (IT) and extended R as first-line treatment in Clinical Cancer Research (in press). This report will update the CR and progression-free survival (PFS) at a median follow-up of 27.1 months (range 0.9–46.1 months). Determination of response and duration of response included a fusion [18 F] fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT) imaging performed at baseline, after the third cycle of CHOP-R, 12 weeks after RIT, then at 6-month intervals for the first three years, and then yearly or at physicians’ discretion. Of the 60 enrolled patients, 55 completed all protocol therapy. The continuous CR rate for all enrolled patients by PET-CT is 73%. The median PFS for all enrolled patients is 38.3 months. To date, 11(18%) patients have relapsed at 7.8–38.3 months. Ten of 11 relapses were among the 35 patients who had positive bone marrow biopsies (28.6%) compared to 1 relapse among the 25 (4.0%) with negative biopsies. Eight of 18 patients with a positive PET scan after CHOP-R have relapsed compared to only 3 relapses of 37 patients with a negative PET scan after CHOP-R. Nine of 10 available relapse tissue biopsies showed FL, and one showed transformation to a diffuse large B-cell lymphoma. Seven patients have been diagnosed with a second malignancy: 1 uterine cancer, 1 colon cancer, 1 prostate cancer, 1 breast cancer, 1 lung cancer, 1 pancreatic cancer, and 1 T-cell lymphoma. There have not been any cases of myelodysplastic syndrome or acute myeloid leukemia. Conclusions: Short course CHOP-R followed by IT and extended R results in high CR rate. However, despite achieving a CR after IT, positive bone marrow involvement at baseline (p Relapsed Patient Grade Stage Flipi Risk Bulk (cm) Bone Marrow Pet Post CHOP Pet Post RIT Time (months) to Progression Relapse Biopsy 1 2 IV 2 3.4 + Pos Neg 13.5 Follicular 2 2 IV 3 5.8 + Pos Neg 21.8 Follicular 3 3 IV 2 14 + Pos Neg 31.2 Follicular 4 3 IV 3 13.5 + Pos Pos 7.8 Follicular 5 2 III 2 7.1 – Pos Neg 38.3 Follicular 6 1 IV 3 4.8 + Neg Neg 27.8 Follicular 7 1 IV 3 6 + Neg Neg 17.2 Follicular 8 N/A IV 3 4.2 + Neg Neg 20.0 N/A 9 2 IV 4 7.4 + Pos Pos 13.6 Large Cell 10 1 IV 2 7 + Pos Neg 14.0 Follicular 11 2 IV 3 3.8 + Pos Neg 9.3 Follicular