Patterns of inpatient antibiotic use among public hospitals in Hong Kong from 2000 to 2015

Background: Studies have demonstrated that higher rates of antibiotic resistance are found in countries with higher antibiotic consumption. The global increase in antibiotic consumption is a major public health concern. Objectives: To describe the antibiotic dispensing patterns in public hospitals in Hong Kong from 2000-2015. Methods: We acquired data on all hospital admissions with any antibiotics dispensed from 2000-2015 from the Hong Kong public hospitals. The annual proportion of hospital admissions with antibiotic dispensed was estimated and stratified by age group. An interrupted time series analysis was conducted to examine any potential change in tetracycline dispensing after the release of the new clinical practice guideline. Results: A total of 35,535,506 antibiotic prescriptions were dispensed among 2,161,360 unique hospitalized patients from 2000 to 2015. Antibiotics were dispensed in 29.2% of all hospital admissions in the public hospitals, the annual proportions of hospital admissions with antibiotics dispensed increased over the study period from 27.87% in 2000 to 31.39% in 2015, ranging from 27.17 to 31.39%. However, a significant increase was only observed in age groups of 5-19, 20-44 and 85 years or above when stratifying by age. In the interrupted time series analysis, a change in trend was detected for tetracycline dispensing which coincided with the time of publication of the new clinical practice guideline. Conclusions: We found that the overall volume of antibiotic use increased between 2000 and 2015. The rise in dispensing of carbapenems in our study is concerning. The significant change in tetracycline use after being recommended as one of the preferred regimens demonstrated that the change in clinical practice guideline had an immediate effect on the antibiotic prescribing practice in Hong Kong public hospitals

Historical photogrammetry: Bird's Paluxy River dinosaur chase sequence digitally reconstructed as it was prior to excavation 70 years ago.

It is inevitable that some important specimens will become lost or damaged over time, conservation is therefore of vital importance. The Paluxy River dinosaur tracksite is among the most famous in the world. In 1940, Roland T. Bird described and excavated a portion of the site containing associated theropod and sauropod trackways. This excavated trackway was split up and housed in different institutions, and during the process a portion was lost or destroyed. We applied photogrammetric techniques to photographs taken by Bird over 70 years ago, before the trackway was removed, to digitally reconstruct the site as it was prior to excavation. The 3D digital model offers the opportunity to corroborate maps drawn by R.T. Bird when the tracksite was first described. More broadly, this work demonstrates the exciting potential for digitally recreating palaeontological, geological, or archaeological specimens that have been lost to science, but for which photographic documentation exists

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC

Preserving Differential Privacy in Convolutional Deep Belief Networks

The remarkable development of deep learning in medicine and healthcare domain presents obvious privacy issues, when deep neural networks are built on users' personal and highly sensitive data, e.g., clinical records, user profiles, biomedical images, etc. However, only a few scientific studies on preserving privacy in deep learning have been conducted. In this paper, we focus on developing a private convolutional deep belief network (pCDBN), which essentially is a convolutional deep belief network (CDBN) under differential privacy. Our main idea of enforcing epsilon-differential privacy is to leverage the functional mechanism to perturb the energy-based objective functions of traditional CDBNs, rather than their results. One key contribution of this work is that we propose the use of Chebyshev expansion to derive the approximate polynomial representation of objective functions. Our theoretical analysis shows that we can further derive the sensitivity and error bounds of the approximate polynomial representation. As a result, preserving differential privacy in CDBNs is feasible. We applied our model in a health social network, i.e., YesiWell data, and in a handwriting digit dataset, i.e., MNIST data, for human behavior prediction, human behavior classification, and handwriting digit recognition tasks. Theoretical analysis and rigorous experimental evaluations show that the pCDBN is highly effective. It significantly outperforms existing solutions

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

Seeing Tree Structure from Vibration

Humans recognize object structure from both their appearance and motion; often, motion helps to resolve ambiguities in object structure that arise when we observe object appearance only. There are particular scenarios, however, where neither appearance nor spatial-temporal motion signals are informative: occluding twigs may look connected and have almost identical movements, though they belong to different, possibly disconnected branches. We propose to tackle this problem through spectrum analysis of motion signals, because vibrations of disconnected branches, though visually similar, often have distinctive natural frequencies. We propose a novel formulation of tree structure based on a physics-based link model, and validate its effectiveness by theoretical analysis, numerical simulation, and empirical experiments. With this formulation, we use nonparametric Bayesian inference to reconstruct tree structure from both spectral vibration signals and appearance cues. Our model performs well in recognizing hierarchical tree structure from real-world videos of trees and vessels.Comment: ECCV 2018. The first two authors contributed equally to this work. Project page: http://tree.csail.mit.edu

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved

Degenerate Rotating Black Holes, Chiral CFTs and Fermi Surfaces I - Analytic Results for Quasinormal Modes

In this work we discuss charged rotating black holes in $AdS_5 \times S^5$ that degenerate to extremal black holes with zero entropy. These black holes have scaling properties between charge and angular momentum similar to those of Fermi surface operators in a subsector of $\mathcal{N}=4$ SYM. We add a massless uncharged scalar to the five dimensional supergravity theory, such that it still forms a consistent truncation of the type IIB ten dimensional supergravity and analyze its quasinormal modes. Separating the equation of motion to a radial and angular part, we proceed to solve the radial equation using the asymptotic matching expansion method applied to a Heun equation with two nearby singularities. We use the continued fraction method for the angular Heun equation and obtain numerical results for the quasinormal modes. In the case of the supersymmetric black hole we present some analytic results for the decay rates of the scalar perturbations. The spectrum of quasinormal modes obtained is similar to that of a chiral 1+1 CFT, which is consistent with the conjectured field-theoretic dual. In addition, some of the modes can be found analytically.Comment: 41 pages, 1 figure, LaTeX; v2: typos corrected, references adde

Normal modes and discovery of high-order cross-frequencies in the DBV white dwarf GD 358

We present a detailed mode identification performed on the 1994 Whole Earth Telescope (WET) run on GD 358. The results are compared with that obtained for the same star from the 1990 WET data. The two temporal spectra show very few qualitative differences, although amplitude changes are seen in most modes, including the disappearance of the mode identified as k=14 in the 1990 data. The excellent coverage and signal-to-noise ratio obtained during the 1994 run lead to the secure identification of combination frequencies up to fourth order, i.e. peaks that are sums or differences of up to four parent frequencies, including a virtually complete set of second-order frequencies, as expected from harmonic distortion. We show how the third-order frequencies are expected to affect the triplet structure of the normal modes by back-interacting with them. Finally, a search for ℓ=2 modes was unsuccessful, not verifying the suspicion that such modes had been uncovered in the 1990 data set