The role of temperature in the detection and diagnosis of neutropenic sepsis in adult solid tumour cancer patients receiving chemotherapy

© 2018 Elsevier Ltd Purpose: The primary aim of this study was to examine the value of temperature as a diagnostic and prognostic indicator of infection and sepsis in neutropenic patients. A secondary aim was to gain insight into the presenting symptoms reported by these patients at home or on their initial admission assessment. Methods: A cohort study was carried out using a case note review of 220 emergency admissions to a regional cancer centre. All participants were neutropenic and were diagnosed with infection on admission. The main outcome measures were relationships between Early Warning Scores and temperature values at home, on admission and during the hospital stay. Results: 22% of patients who became acutely unwell did not have a fever. Pearson correlations showed only small associations between highest temperature value at any time point and highest early warning scores (r(202) = 0.176, P =.012). Temperature at home (B = 0.156, P =.336) and temperature on admission (B = 0.200, P =.052) did not predict highest Early Warning Scores. Conclusions: Body temperature is not a consistently reliable diagnostic or prognostic indicator for outcomes in patients with neutropenia and symptoms of infection. It can assist with early presentation and recognition of infection in many neutropenic patients. However, over-reliance on temperature risks missing the opportunity for early detection and treatment

Mutation-enrichment next-generation sequencing for quantitative detection of KRAS mutations in urine cell-free DNA from patients with advanced cancers

Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRASExperimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer.Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03).Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure

Why has research in face recognition progressed so slowly? The importance of variability

Despite many years of research, there has been surprisingly little progress in our understanding of how faces are identified. Here I argue that there are two contributory factors: (a) Our methods have obscured a critical aspect of the problem, within-person variability; and (b) research has tended to conflate familiar and unfamiliar face processing. Examples of procedures for studying variability are given, and a case is made for studying real faces, of the type people recognize every day. I argue that face recognition (specifically identification) may only be understood by adopting new techniques that acknowledge statistical patterns in the visual environment. As a consequence, some of our current methods will need to be abandoned

Potential health and economic impacts of dexamethasone treatment for patients with COVID-19

Acknowledgements We thank all members of the COVID-19 International Modelling Consortium and their collaborative partners. This work was supported by the COVID-19 Research Response Fund, managed by the Medical Sciences Division, University of Oxford. L.J.W. is supported by the Li Ka Shing Foundation. R.A. acknowledges funding from the Bill and Melinda Gates Foundation (OPP1193472).Peer reviewedPublisher PD

Non-minimal coupling of the scalar field and inflation

We study the prescriptions for the coupling constant of a scalar field to the Ricci curvature of spacetime in specific gravity and scalar field theories. The results are applied to the most popular inflationary scenarios of the universe; their theoretical consistency and certain observational constraints are discussed.Comment: 23 pages, LaTex, no figures, to appear in Physical Review

Characteristics of the nuclear (18S, 5.8S, 28S and 5S) and mitochondrial (12S and 16S) rRNA genes of Apis mellifera (Insecta: Hymenoptera): structure, organization, and retrotransposable elements

As an accompanying manuscript to the release of the honey bee genome, we report the entire sequence of the nuclear (18S, 5.8S, 28S and 5S) and mitochondrial (12S and 16S) ribosomal RNA (rRNA)-encoding gene sequences (rDNA) and related internally and externally transcribed spacer regions of Apis mellifera (Insecta: Hymenoptera: Apocrita). Additionally, we predict secondary structures for the mature rRNA molecules based on comparative sequence analyses with other arthropod taxa and reference to recently published crystal structures of the ribosome. In general, the structures of honey bee rRNAs are in agreement with previously predicted rRNA models from other arthropods in core regions of the rRNA, with little additional expansion in non-conserved regions. Our multiple sequence alignments are made available on several public databases and provide a preliminary establishment of a global structural model of all rRNAs from the insects. Additionally, we provide conserved stretches of sequences flanking the rDNA cistrons that comprise the externally transcribed spacer regions (ETS) and part of the intergenic spacer region (IGS), including several repetitive motifs. Finally, we report the occurrence of retrotransposition in the nuclear large subunit rDNA, as R2 elements are present in the usual insertion points found in other arthropods. Interestingly, functional R1 elements usually present in the genomes of insects were not detected in the honey bee rRNA genes. The reverse transcriptase products of the R2 elements are deduced from their putative open reading frames and structurally aligned with those from another hymenopteran insect, the jewel wasp Nasonia (Pteromalidae). Stretches of conserved amino acids shared between Apis and Nasonia are illustrated and serve as potential sites for primer design, as target amplicons within these R2 elements may serve as novel phylogenetic markers for Hymenoptera. Given the impending completion of the sequencing of the Nasonia genome, we expect our report eventually to shed light on the evolution of the hymenopteran genome within higher insects, particularly regarding the relative maintenance of conserved rDNA genes, related variable spacer regions and retrotransposable elements

Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients