Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study

OBJECTIVES: Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. METHODS: Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/μL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. RESULTS: In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/μL, and 95% had advanced HIV (CD4 count < 200 cells/μL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. CONCLUSIONS: There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services

Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis

BACKGROUND: The C - reactive protein (CRP) response is often measured in patients with active tuberculosis (TB) yet little is known about its relationship to clinical features in TB, or whether responses differ between ethnic groups or with different Mycobacterium tuberculosis (M.tb) strain types. We report the relationship between baseline serum CRP prior to treatment and disease characteristics in a metropolitan population with TB resident in a low TB incidence region. METHODS: People treated for TB at four London, UK sites between 2003 and 2014 were assessed and data collected on the following characteristics: baseline CRP level; demographics (ethnicity, gender and age); HIV status; site of TB disease; sputum smear (in pulmonary cases) and culture results. The effect of TB strain-type was also assessed in culture-positive pulmonary cases using VNTR typing data. RESULTS: Three thousands two hundred twenty-two patients were included in the analysis of which 72 % had a baseline CRP at or within 4 weeks prior to starting TB treatment. CRP results were significantly higher in culture positive cases compared to culture negative cases: median 49 mg/L (16-103 mg/L) vs 19 mg/L (IQR 5-72 mg/L), p = <0.001. In those with pulmonary disease, smear positive cases had a higher CRP than smear negative cases: 67 mg/L (31-122 mg/L) vs 24 mg/L (7-72 mg/L), p < 0.001. HIV positive cases had higher baseline CRPs than HIV negative cases: 75 mg/L (26-136 mg/L) vs 37 mg/L (10-88 mg/L), p <0.001. Differing sites of disease were associated with differences in baseline CRP: locations that might be expected to have a high mycobacterial load (e.g. pulmonary disease and disseminated disease) had a significantly higher CRP than those such as skin, lymph node or CNS disease, where the mycobacterial load is typically low in HIV negative subjects. In a multivariable log-scale linear regression model adjusting for host characteristics and M.tb strain type, infection with the East African Indian strain was associated with significantly lower baseline-CRP (fold-change in CRP 0.51 (0.34-0.77), p < 0.01). CONCLUSIONS: Host and mycobacterial factors are strongly associated with baseline CRP response in tuberculosis. This analysis suggests that there are important differences in innate immune response according to ethnicity, Mtb strain type and site of disease. This may reflect differing mycobacterial loads or host immune responses

The Canonical Model of a Singular Curve

We give refined statements and modern proofs of Rosenlicht's results about the canonical model C' of an arbitrary complete integral curve C. Notably, we prove that C and C' are birationally equivalent if and only if C is nonhyperelliptic, and that, if C is nonhyperelliptic, then C' is equal to the blowup of C with respect to the canonical sheaf \omega. We also prove some new results: we determine just when C' is rational normal, arithmetically normal, projectively normal, and linearly normal.Comment: 28 pages, no figures, IV Congresso Iberoamericano de Geometria Complex

Ultrametric spaces of branches on arborescent singularities

Let $S$ be a normal complex analytic surface singularity. We say that $S$ is arborescent if the dual graph of any resolution of it is a tree. Whenever $A,B$ are distinct branches on $S$, we denote by $A \cdot B$ their intersection number in the sense of Mumford. If $L$ is a fixed branch, we define $U_L(A,B)= (L \cdot A)(L \cdot B)(A \cdot B)^{-1}$ when $A \neq B$ and $U_L(A,A) =0$ otherwise. We generalize a theorem of P{\l}oski concerning smooth germs of surfaces, by proving that whenever $S$ is arborescent, then $U_L$ is an ultrametric on the set of branches of $S$ different from $L$. We compute the maximum of $U_L$, which gives an analog of a theorem of Teissier. We show that $U_L$ encodes topological information about the structure of the embedded resolutions of any finite set of branches. This generalizes a theorem of Favre and Jonsson concerning the case when both $S$ and $L$ are smooth. We generalize also from smooth germs to arbitrary arborescent ones their valuative interpretation of the dual trees of the resolutions of $S$. Our proofs are based in an essential way on a determinantal identity of Eisenbud and Neumann.Comment: 37 pages, 16 figures. Compared to the first version on Arxiv, il has a new section 4.3, accompanied by 2 new figures. Several passages were clarified and the typos discovered in the meantime were correcte

Local alignment of generalized k-base encoded DNA sequence

<p>Abstract</p> <p>Background</p> <p>DNA sequence comparison is a well-studied problem, in which two DNA sequences are compared using a weighted edit distance. Recent DNA sequencing technologies however observe an encoded form of the sequence, rather than each DNA base individually. The encoded DNA sequence may contain technical errors, and therefore encoded sequencing errors must be incorporated when comparing an encoded DNA sequence to a reference DNA sequence.</p> <p>Results</p> <p>Although two-base encoding is currently used in practice, many other encoding schemes are possible, whereby two ore more bases are encoded at a time. A generalized <it>k</it>-base encoding scheme is presented, whereby feasible higher order encodings are better able to differentiate errors in the encoded sequence from true DNA sequence variants. A generalized version of the previous two-base encoding DNA sequence comparison algorithm is used to compare a <it>k</it>-base encoded sequence to a DNA reference sequence. Finally, simulations are performed to evaluate the power, the false positive and false negative SNP discovery rates, and the performance time of <it>k</it>-base encoding compared to previous methods as well as to the standard DNA sequence comparison algorithm.</p> <p>Conclusions</p> <p>The novel generalized <it>k</it>-base encoding scheme and resulting local alignment algorithm permits the development of higher fidelity ligation-based next generation sequencing technology. This bioinformatic solution affords greater robustness to errors, as well as lower false SNP discovery rates, only at the cost of computational time.</p

Streaming fragment assignment for real-time analysis of sequencing experiments

We present eXpress, a software package for efficient probabilistic assignment of ambiguously mapping sequenced fragments. eXpress uses a streaming algorithm with linear run time and constant memory use. It can determine abundances of sequenced molecules in real time and can be applied to ChIP-seq, metagenomics and other large-scale sequencing data. We demonstrate its use on RNA-seq data and show that eXpress achieves greater efficiency than other quantification methods

Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit

Global epidemiological data regarding outcomes for patients in intensive care units (ICUs) are scarce, but are important in understanding the worldwide burden of critical illness. We, therefore, did an international audit of ICU patients worldwide and assessed variations between hospitals and countries in terms of ICU mortality

PUGeo-Net: A Geometry-centric Network for 3D Point Cloud Upsampling

This paper addresses the problem of generating uniform dense point clouds to describe the underlying geometric structures from given sparse point clouds. Due to the irregular and unordered nature, point cloud densification as a generative task is challenging. To tackle the challenge, we propose a novel deep neural network based method, called PUGeo-Net, that learns a $3\times 3$ linear transformation matrix $\bf T$ for each input point. Matrix $\mathbf T$ approximates the augmented Jacobian matrix of a local parameterization and builds a one-to-one correspondence between the 2D parametric domain and the 3D tangent plane so that we can lift the adaptively distributed 2D samples (which are also learned from data) to 3D space. After that, we project the samples to the curved surface by computing a displacement along the normal of the tangent plane. PUGeo-Net is fundamentally different from the existing deep learning methods that are largely motivated by the image super-resolution techniques and generate new points in the abstract feature space. Thanks to its geometry-centric nature, PUGeo-Net works well for both CAD models with sharp features and scanned models with rich geometric details. Moreover, PUGeo-Net can compute the normal for the original and generated points, which is highly desired by the surface reconstruction algorithms. Computational results show that PUGeo-Net, the first neural network that can jointly generate vertex coordinates and normals, consistently outperforms the state-of-the-art in terms of accuracy and efficiency for upsampling factor $4\sim 16$.Comment: 17 pages, 10 figure

Mean-Field HP Model, Designability and Alpha-Helices in Protein Structures

Analysis of the geometric properties of a mean-field HP model on a square lattice for protein structure shows that structures with large number of switch backs between surface and core sites are chosen favorably by peptides as unique ground states. Global comparison of model (binary) peptide sequences with concatenated (binary) protein sequences listed in the Protein Data Bank and the Dali Domain Dictionary indicates that the highest correlation occurs between model peptides choosing the favored structures and those portions of protein sequences containing alpha-helices.Comment: 4 pages, 2 figure