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Summary Background Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department. Methods Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities. Findings A three-gene transcript signature, comprising HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0·976 (95% CI 0·919−1·000), sensitivity of 97·3% (85·8−99·9), and specificity of 100% (63·1−100). The AUROC for C-reactive protein (CRP) was 0·833 (0·694−0·944) and for leukocyte count was 0·938 (0·840−0·986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte count for discriminating viral infections from all other infections. In the second validation analysis, which included SARS-CoV-2-positive participants, the signature discriminated 35 bacterial infections from 34 SARS-CoV-2-positive COVID-19 infections with AUROC of 0·953 (0·893−0·992), sensitivity 88·6%, and specificity of 94·1%. Interpretation This novel three-gene signature discriminates viral infections, including COVID-19, from other emergency infection presentations in adults, outperforming both leukocyte count and CRP, thus potentially providing substantial clinical utility in managing acute presentations with infection. Funding National Institute for Health Research, Medical Research Council, Wellcome Trust, and EU-FP7.

This compendium is a follow-up to the 2018 American Diabetes Association compendium Diagnosis and Management of Diabetic Foot Complications. Whereas the first compendium offered a broad general overview of diabetic foot conditions, this second volume presents a detailed discussion of the prevention and treatment of diabetic foot infections (DFIs), a major contributor to high amputation rates among people with diabetes. The treatise begins from the viewpoint of basic science, describing the impact of infection on the healing process of experimental wounds. There follow overviews of biofilm development in chronic diabetic foot ulcers (DFUs), the microbiology of DFIs, and the crucial role of debridement in ensuring positive outcomes of DFI treatment. Next, the authors provide a practical guide to the diagnosis and clinical management of DFIs. Current controversies regarding the treatment of osteomyelitis are addressed, including the relative value of antibiotics versus surgery and the use of intravenous versus oral antibiotics. The compendium closes with a look at new topical treatments and the role of emerging technologies in infection control.This publication has been supported by unrestricted educational grants to the American Diabetes Association from Healogics, Inc., and Organogenesis, Inc.The opinions expressed are those of the authors and do not necessarily reflect those of Healogics, Inc., Organogenesis, Inc., or the American Diabetes Association. The content was developed by the authors and does not represent the policy or position of the American Diabetes Association, any of its boards or committees, or any of its journals or their editors or editorial boards.

There is a critical need for improved infectious disease diagnostics to enable rapid case identification in a viral pandemic and support targeted antimicrobial prescribing. Here we use high-resolution liquid chromatography coupled with mass spectrometry to compare the admission serum metabolome of patients attending hospital with a range of viral infections, including SARS-CoV-2, to those with bacterial infections, non-infected inflammatory conditions and healthy controls. We demonstrate for the first time that 3’-Deoxy-3’,4’-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), is detectable in serum. ddhC acts as an accurate biomarker for viral infections, generating an area under the receiver operating characteristic curve of 0.954 (95% confidence interval 0.923-0.986) when comparing viral to non-viral cases. Gene expression of viperin, the enzyme responsible for ddhCTP synthesis, is highly correlated with ddhC, providing a biological mechanism for its increase during viral infection. These findings underline a key future diagnostic role of ddhC in the context of pandemic preparedness and antimicrobial stewardship.

Transparent resistive switching random access memory (ReRAM) is of interest for the future integrated invisible circuitry. However, poor understanding of its working mechanism in transparent ReRAMs with the indium tin oxide (ITO) electrode is still a critical problem and will hinder its widespread applications. To reveal the actual working mechanism in transparent ReRAMs with the ITO electrode, we investigate the transparent ITO/SiOx/ITO memory devices (∼82% transmittance in the visible region) and compare it with ITO/SiOx/Au memory devices, which both can exhibit reproducible bipolar switching. The indium (In) filament evolution, which accounts for the bipolar switching behaviors in the ITO/SiOx/ITO (or Au) memories, is directly observed using transmission electron microscopy on samples with different memory states (electroformed, ON, and OFF). These studies uncover the microscopic mechanism behind the bipolar switching in SiOx-based ReRAM devices with the ITO electrode, providing a general guidance for the design of high-performance ReRAMs with large scalability and high endurance. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) This work is supported by the National Research Foundation Competitive Research Programme (grant no. NRF-CRP13- 2014-02) and the RIE2020 ASTAR AME IAF-ICP Grant (No. I1801E0030). K.Q. acknowledges the “Qilu young scholar” program (grant no. 11500089963022) of Shandong University, China.

Publisher's version (útgefin grein), Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18., Competing interests Gad Getz receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER. Hikmat Al-Ahmadie is consultant for AstraZeneca and Bristol-Myers Squibb. Samuel Aparicio is a founder and shareholder of Contextual Genomics. Pratiti Bandopadhayay receives grant funding from Novartis for an unrelated project. Rameen Beroukhim owns equity in Ampressa Therapeutics. Andrew Biankin receives grant funding from Celgene, AstraZeneca and is a consultant for or on advisory boards of AstraZeneca, Celgene, Elstar Therapeutics, Clovis Oncology and Roche. Ewan Birney is a consultant for Oxford Nanopore, Dovetail and GSK. Marcus Bosenberg is a consultant for Eli Lilly. Atul Butte is a cofounder of and consultant for Personalis, NuMedii, a consultant for Samsung, Geisinger Health, Mango Tree Corporation, Regenstrief Institute and in the recent past a consultant for 10x Genomics and Helix, a shareholder in Personalis, a minor shareholder in Apple, Twitter, Facebook, Google, Microsoft, Sarepta, 10x Genomics, Amazon, Biogen, CVS, Illumina, Snap and Sutro and has received honoraria and travel reimbursement for invited talks from Genentech, Roche, Pfizer, Optum, AbbVie and many academic institutions and health systems. Carlos Caldas has served on the Scientific Advisory Board of Illumina. Lorraine Chantrill acted on an advisory board for AMGEN Australia in the past 2 years. Andrew D. Cherniack receives research funding from Bayer. Helen Davies is an inventor on a number of patent applications that encompass the use of mutational signatures. Francisco De La Vega was employed at Annai Systems during part of the project. Ronny Drapkin serves on the scientific advisory board of Repare Therapeutics and Siamab Therapeutics. Rosalind Eeles has received an honorarium for the GU-ASCO meeting in San Francisco in January 2016 as a speaker, a honorarium and support from Janssen for the RMH FR meeting in November 2017 as a speaker (title: genetics and prostate cancer), a honorarium for an University of Chicago invited talk in May 2018 as speaker and an educational honorarium paid by Bayer & Ipsen to attend GU Connect ‘Treatment sequencing for mCRPC patients within the changing landscape of mHSPC’ at a venue at ESMO, Barcelona, on 28 September 2019. Paul Flicek is a member of the scientific advisory boards of Fabric Genomics and Eagle Genomics. Ronald Ghossein is a consultant for Veracyte. Dominik Glodzik is an inventor on a number of patent applications that encompass the use of mutational signatures. Eoghan Harrington is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Yann Joly is responsible for the Data Access Compliance Office (DACO) of ICGC 2009-2018. Sissel Juul is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Vincent Khoo has received personal fees and non-financial support from Accuray, Astellas, Bayer, Boston Scientific and Janssen. Stian Knappskog is a coprincipal investigator on a clinical trial that receives research funding from AstraZeneca and Pfizer. Ignaty Leshchiner is a consultant for PACT Pharma. Carlos López-Otín has ownership interest (including stock and patents) in DREAMgenics. Matthew Meyerson is a scientific advisory board chair of, and consultant for, OrigiMed, has obtained research funding from Bayer and Ono Pharma and receives patent royalties from LabCorp. Serena Nik-Zainal is an inventor on a number of patent applications that encompass the use of mutational signatures. Nathan Pennell has done consulting work with Merck, Astrazeneca, Eli Lilly and Bristol-Myers Squibb. Xose S. Puente has ownership interest (including stock and patents in DREAMgenics. Benjamin J. Raphael is a consultant for and has ownership interest (including stock and patents) in Medley Genomics. Jorge Reis-Filho is a consultant for Goldman Sachs and REPARE Therapeutics, member of the scientific advisory board of Volition RX and Paige.AI and an ad hoc member of the scientific advisory board of Ventana Medical Systems, Roche Tissue Diagnostics, InVicro, Roche, Genentech and Novartis. Lewis R. Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest, RedHill Biopharma, Target PharmaSolutions and Wako Diagnostics and has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics and TAVEC Pharmaceuticals. Richard A. Scolyer has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia, Myriad, NeraCare GmbH and Amgen. Tal Shmaya is employed at Annai Systems. Reiner Siebert has received speaker honoraria from Roche and AstraZeneca. Sabina Signoretti is a consultant for Bristol-Myers Squibb, AstraZeneca, Merck, AACR and NCI and has received funding from Bristol-Myers Squibb, AstraZeneca, Exelixis and royalties from Biogenex. Jared Simpson has received research funding and travel support from Oxford Nanopore Technologies. Anil K. Sood is a consultant for Merck and Kiyatec, has received research funding from M-Trap and is a shareholder in BioPath. Simon Tavaré is on the scientific advisory board of Ipsen and a consultant for Kallyope. John F. Thompson has received honoraria and travel support for attending advisory board meetings of GlaxoSmithKline and Provectus and has received honoraria for participation in advisory boards for MSD Australia and BMS Australia. Daniel Turner is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Naveen Vasudev has received speaker honoraria and/or consultancy fees from Bristol-Myers Squibb, Pfizer, EUSA pharma, MSD and Novartis. Jeremiah A. Wala is a consultant for Nference. Daniel J. Weisenberger is a consultant for Zymo Research. Dai-Ying Wu is employed at Annai Systems. Cheng-Zhong Zhang is a cofounder and equity holder of Pillar Biosciences, a for-profit company that specializes in the development of targeted sequencing assays. The other authors declare no competing interests.

Background.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success.Methods.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy.Results.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using β-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with β-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34).Conclusions.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of β-lactams are confirmed and maybe also a potential benefit from adding rifampin.

Background: England is experiencing scarlet fever activity unprecedented in modern times. In 2016, England's scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular-epidemiological investigation of these events and emergence of a new emm1 lineage. Methods: We analysed changes in S. pyogenes emm-genotypes, and notifications of scarlet fever and invasive disease 2014-2016 using regional and national data. We analysed genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-2016, and compared 2800 global emm1 sequences. Expression of Streptococcal pyrogenic exotoxin (Spe)A by sequenced non-invasive emm1 isolates was quantified. Findings: Coincident with national increases in scarlet fever and invasive disease, emm1 S. pyogenes infections increased significantly, accounting for 32·6% (47/144) of pharyngeal isolates in North West London and 41·9% (267/637) of invasive isolates nationally in March-May 2016. Sequences of emm1 isolates from 2009-2016 demonstrated emergence of a new emm1 lineage (M1UK), with overlap of pharyngitis, scarlet fever, and invasive M1UK strains, that could be genotypically distinguished from pandemic emm1 isolates (M1global). Compared with M1global , median expression of SpeA increased 9-fold in M1UK isolates. M1UK expanded nationally to represent 84% (252/299) of all emm1, genomes in 2016; analysis identified two M1UK isolates outside the UK. Interpretation: A dominant new emm1 S. pyogenes lineage characterized by increased SpeA production has emerged during increased S. pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S. pyogenes provide plausible explanation for increased invasive disease, and rationale for global surveillance. Funding Statement: Supported by grants from Medical Research Council (MR/P022669/1); NIHR Health Protection Unit in AMR and HCAI (HPRU-2012-10047); NIHR BRC SpyVAC; Conor Kerin Foundation. NNL is a Sir Henry Wellcome Postdoctoral Research Fellow funded by the Wellcome Trust (103197/Z/13/Z); EJ is a Rosetrees/Stoneygate 2017 Imperial College Research Fellow (M683). Declaration of Interests: JP is a consultant to Next Gen Diagnostics LLC; other authors declare no interests. Ethics Approval Statement: Clinical data were linked to isolates and anonymized in accordance with Research Ethics approval 06/Q0406/20.

We report a p-type nickel oxide/n-type indium gallium zinc oxide (p-NiO/n-IGZO) thin film heterojunction structure for resistive switching memory application. The as-fabricated structure exhibits the normal p-n junction behaviors with good rectification characteristic. The structure is turned into a bipolar resistive switching memory by a forming process in which the p-n junction is reversely biased. The device shows good memory performances; and it has the capability of multibit storage, which can be realized by controlling the compliance current or reset stop voltage during the switching operation. The mechanisms for both the forming process and bipolar resistive switching are discussed; and the current conduction at the low- and high-resistance states are examined in terms of temperature dependence of the current-voltage characteristic of the structure. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore)

Background: Bone and joint infections are becoming increasingly common and are usually treated with surgery and a course of intravenous antibiotics. However, there is no evidence to support the superiority of intravenous therapy and there is a growing body of literature showing that oral therapy is effective in treating these infections. Given this lack of evidence the clinical trial ‘Oral Versus Intravenous Antibiotics’ (OVIVA) was designed to assess the clinical and cost-effectiveness of intravenous versus oral antibiotics for the treatment of bone and joint infections, using a non-inferiority design. Clinical results from the trial indicate that oral antibiotics are non-inferior to intravenous antibiotics. The aim of this paper is to evaluate the cost-effectiveness of intravenous compared to oral antibiotics for treating bone and joint infections, using data from OVIVA. Methods: A cost-utility analysis was carried out, the main economic outcome measure was the quality adjusted life-year, measured using the EQ-5D-3L questionnaire, combined with costs to estimate cost-effectiveness over 12-months follow-up. Results: Results show that costs were significantly lower in the oral arm compared to the intravenous arm, a difference of £2,740 (95% confidence interval £1,488 to £3,992). Results of four sensitivity analyses were consistent with the base-case results. QALYs were marginally higher in the oral arm, however this difference was not statistically significant; -0.007 (95% confidence interval -0.045 to 0.031). Conclusions: Treating patients with bone and joint infections for the first six weeks of therapy with oral antibiotics is both less costly and does not result in detectable differences in quality of life compared to treatment with intravenous antibiotics. Adopting a practice of treating bone and joint infections with oral antibiotics early in the course of therapy could potentially save the UK National Health Service over £17 million annually.

To compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system.In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis.The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×10Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.

Multilevel high-resistance states are achieved in TiN/HfO x /Pt resistive switching random access memory device by controlling the reset stop voltage. Impedance spectroscopy is used to study the multilevel high-resistance states. It is shown that the high-resistance states can be described with an equivalent circuit consisting of the major components $R_{s}$ , $R$ , and $C$ corresponding to the series resistance of the TiON interfacial layer, the equivalent parallel resistance, and capacitance of the leakage gap between the TiON layer and the residual conductive filament, respectively. These components show a strong dependence on the stop voltage, which can be explained in the framework of oxygen vacancy model and conductive filament concept. On the other hand, $R$ is observed to decrease with dc bias, which can be attributed to the barrier lowering effect of the Coulombic trap well in the Poole–Frenkel emission model.

The human brain is an extremely complex system of 10

Electronics with multifunctionalities such as transparency, portability, and flexibility are anticipated for future circuitry development. Flexible memory is one of the indispensable elements in a hybrid electronic integrated circuit as the information storage device. Herein, we demonstrate a transparent, flexible, and transferable hexagonal boron nitride (hBN)-based resistive switching memory with indium tin oxide (ITO) and graphene electrodes on soft polydimethylsiloxane (PDMS) substrate. The ITO/hBN/graphene/PDMS memory device not only exhibits excellent performance in terms of optical transmittance (∼85% in the visible wavelength), ON/OFF ratio (∼480), retention time (∼5 × 104 s) but also shows robust flexibility under bending conditions and stable operation on arbitrary substrates. More importantly, direct observation of indium filaments in an ITO/hBN/graphene device is found via ex situ transmission electron microscopy, which provides critical insight on the complex resistive switching mechanisms.

Reactive sputtering has been used to synthesize Al-rich Al2O3 thin films. After post-deposition thermal annealing, the excess Al content forms Al nanocrystals (nc-Al) which are dispersed in the Al2O3 matrix. In the Al/Al-rich Al2O3/p-Si structure, the current conduction which follows a Schottky emission process can be greatly enhanced by a charging process with negative voltage pulses and then maintained for considerable duration, realizing write-once-read-many-times (WORM) memory behaviors. The current conduction enhancement is attributed to the reduction of effective Schottky barrier caused by charging-induced hole trapping in the nc-Al related defects near the oxide/p-Si interface. It is found that the sample with lower concentration of nc-Al has a larger memory window due to the lower initial current. In addition, the retention is also better since the release of trapped charges is more difficult with less nc-Al related leakage paths present in the oxide film. The concentration of excess Al content in the Al-rich Al2O3 thin film can be optimized to achieve large memory windows as well as good retention characteristics in the associated WORM memory devices.

Neuron thin-film transistors (TFTs) with coplanar control gates based on RF sputtering-deposited amorphous indium-gallium-zinc oxide (IGZO) layer are fabricated. Two coplanar control gates, capacitively coupled with the floating gate, can effectively control the neutron TFT. The drain current of the TFT can be controlled by the logic states (and the voltage magnitude) of the control gates, which is attributed to the modulation of an electron accumulation region in the IGZO channel layer. The neuron TFT can produce three output states, which could be used to implement an abacuslike counting scheme. It can also be used to implement the OR and AND logic functions on the same device. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore)

Background: Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3–5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis. Method: Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010–January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May–December 2011). Results: Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage. Conclusions: Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.

CNx films were prepared on cemented carbide substrates by a pulsed bias arc ion-plating method with two graphite targets and using N2/Ar mixture gases. The effects of the deposition parameters, such as substrate negative-bias voltage, duty cycle, and nitrogen flow rate, on the structures and properties of CNx films were investigated using Raman spectra and nanoindentation. The properties of CNx films are closely related to the film structures. For CNx films deposited at a different bias voltage, the CNx film deposited at a bias voltage of −300 V had the highest hardness. The ID/IG ratio and G peak position decreased and then increased with increasing bias voltage, and the minimum values, which correspond to the highest sp3 content, were obtained at a bias voltage of −300 V. For the CNx films deposited at different duty cycles, the hardness and elastic modulus decreased with increasing duty cycle. For the CNx films deposited at different nitrogen flow rates, the results show that first the ID/IG ratio decr...

ZrN doped diamondlike carbon composite films with different compositions were deposited on cemented carbide substrates at different nitrogen flow rates by pulsed bias arc ion plating. Scanning electron microscopy results show that the film surfaces were all uniform, smooth, and dense. X-ray photoelectron spectroscopy reveal the C contents are more than 60%, the N content increases, and the Zr content decreases with increasing nitrogen flow rate. The Raman spectra indicated that the deposited films were diamondlike carbon. X-ray diffraction results suggested that a ZrN crystalline phase was also present in the films. The hardness and elastic modulus were closely related to the composition and structure of the films and decrease with increasing nitrogen flow rates, principally due to the increase in the sp2 content and the decrease in the ZrN crystalline phase.

Friction stir welding (FSW) experiments with different panel dimensions and welding parameters have been designed to study the distortion of FSW. The FSW experiments were carried out with a load co...

Lead-free bismuth sodium potassium lithium titanate—barium titanate [0.885 (Bi1/2Na1/2)TiO3-0.05(Bi1/2K1/2)TiO3–0.015(Bi1/2Li1/2)TiO3-0.05BaTiO3, BNKLBT-1.5] fibres have been fabricated by a powder-based extrusion method. The ceramic fibres with 400 μ m diameter were well-crystallized after being calcined at 800°C and sintered at 1170°C. After being poled, the electromechanical coupling coefficient k33 of the fibre is 0.55 while other properties are comparable to those a ceramic disc. The BNKLNT ceramic fibres prepared by the powder-based extrusion method have good piezoelectric and ferroelectric properties and have potential to replace lead zirconate titanate (PZT) fibres in various device applications.

Background Bone and joint infection in adults arises most commonly as a complication of joint replacement surgery, fracture fixation and diabetic foot infection. The associated morbidity can be devastating to patients and costs the National Health Service an estimated £20,000 to £40,000 per patient. Current standard of care in most UK centres includes a prolonged course (4–6 weeks) of intravenous antibiotics supported, if available, by an outpatient parenteral antibiotic therapy service. Intravenous therapy carries with it substantial risks and inconvenience to patients, and the antibiotic-related costs are approximately ten times that of oral therapy. Despite this, there is no evidence to suggest that oral therapy results in inferior outcomes. We hypothesise that, by selecting oral agents with high bioavailability, good tissue penetration and activity against the known or likely pathogens, key outcomes in patients managed primarily with oral therapy are non-inferior to those in patients treated by intravenous therapy. Methods The OVIVA trial is a parallel group, randomised (1:1), un-blinded, non-inferiority trial conducted in thirty hospitals across the UK. Eligible participants are adults (>18 years) with a clinical syndrome consistent with a bone, joint or metalware-associated infection who have received ≤7 days of intravenous antibiotic therapy from the date of definitive surgery (or the start of planned curative therapy in patients treated without surgical intervention). Participants are randomised to receive either oral or intravenous antibiotics, selected by a specialist infection physician, for the first 6 weeks of therapy. The primary outcome measure is definite treatment failure within one year of randomisation, as assessed by a blinded endpoint committee, according to pre-defined microbiological, histological and clinical criteria. Enrolling 1,050 subjects will provide 90 % power to demonstrate non-inferiority, defined as less than 7.5 % absolute increase in treatment failure rate in patients randomised to oral therapy as compared to intravenous therapy (one-sided alpha of 0.05). Discussion If our results demonstrate non-inferiority of orally administered antibiotic therapy, this trial is likely to facilitate a dramatically improved patient experience and alleviate a substantial financial burden on healthcare services. Trial registration ISRCTN91566927 - 14/02/2013 Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1098-y) contains supplementary material, which is available to authorized users.

Antibiotics that are well absorbed after oral administration are available, and the best current evidence suggests they are safe and effective for many conditions. Belief in the superiority of intravenous antibiotics is widespread among health professionals and patients, but it is not supported by good evidence. Expanding the evidence base will provide patients and clinicians with further reassurance in specific situations, but reasons for the belief in the strength of intravenous therapy also need to be understood and addressed. Trials expanding the evidence base might follow noninferiority designs, based on the precedent of widespread intravenous use. For many indications, the theoretical reasons for preferring intravenous therapy are not strong, and the risks of intravenous therapy are well established. It would be more logical for many indications to regard oral antibiotics as the default position and require trial designs to test the superiority of intravenous therapy. Clarity regarding the harms and benefits of intravenous antibiotics is needed. There is potential to change global clinical practice for the better, reducing health care costs and minimizing harm to patients.

The human brain is an extremely complex system of 1010-1011 neurons. To construct brain-like neuromorphic hardware, the neuron unit should be implemented effectively. Here, we report a neuron transistor based on a MoS2 flake, which has summation and threshold functions similar to biological neurons and may act as a basic neuron unit in neuromorphic hardware. The neuron transistor is composed of a floating gate and two control gates. A heavily doped silicon substrate serves as the floating gate, while the two control gates are capacitively coupled with the floating gate. The neuron transistor can be well controlled by the two control gates individually or simultaneously. The drain current can be modulated by the input voltages at the control gates. While the current response of the neuron transistor has a large dependence on the magnitude of the input signal, it shows little dependence on the frequency of the input signal. To demonstrate the potential neuromorphic application of the neuron transistor, functions including abacus-like function, AND logic and OR logic are realized in the neuron transistor.

Mining ion-type rare-earth ore made the landscape and ecological environment degraded in mining area, and the tailing produced by rare-earth mining also led large areas land desertification, which resulted in surface temperature variations and significant differences in other types of mining disturbances. In order to analyse surface disturbance of rare-earth mining area, this paper applied the methods based on Normalized Difference Vegetation Index (NDVI) and Temperature different Coefficient (TDC) as the ecological disturbance indicator, compared and validated their applicability in Lingbei rare-earth mining area of Southern China. The results illustrated that, compared to NDVI, the TDC which reflected the characteristic of rare-earth mining technology has better discrimination of disturbance, especially for in-situ leach mining area. The places of tailing and the in-situ leach mining plants were the most dramatic mining disturbance. They had the biggest TDC value, followed by orchards and farmlands, reclamation plants, they had relatively small disturbance. And the last was the plant with the smallest TDC value. TDC in rare-earth mining could better correspond to the level of surface ecological disturbance. Therefore, TDC as the indicator of ecological disturbance factor had better performance than NDVI in rare-earth mining area.

Objectives. This study examined the effect of childlessness on psychological well-being in widowhood taking into account the influences of social network variables. Method. A total of 273 Chinese widowed individuals who were community dwelling formed the sample of this study. Sixteen percent ( n = 44) were childless. Social network variables, instrumental activities of daily living, chronic illnesses, depressive symptoms, life satisfaction, positive affect, and negative affect were assessed. Results. Childlessness was significantly associated with all outcomes of psychological well-being even after con trolling for network size. After positive and negative exchanges were taken into account, the effect of childlessness on depression and life satisfaction became nonsignificant but remained significant on positive and negative affect. Furthermore, the effects of childlessness on depression and life satisfaction were significantly stronger in women than in men. Childlessness also had a stronger association with depression in those with functional impairments. Discussion. Findings support the importance of children, and supportive exchanges with them, for the subjective well-being of Chinese widowed persons. Being women and having physical dependencies might amplify the effects of childlessness.

The reconfiguration on underground geology system is one of the key techniques for secondary development in Daqing oil field. The geological modeling is the unique method to characterize new knowledge system of reservoir. The development history of maturing field is long. The structure of maturing field is complex and the distribution of oil remaining is highly scattered. The difficulty of adjustment and potential tapping is great. In viewing of demand for secondary development, the strategies and methods of geological modeling are proposed. According to the characteristics that many faults crosscut each other, the clue of fractional simulation—key horizon controlling—overall structural modeling is carried out to accurately and effectively build fine structural models. In order to approximate the real microfacies simulation effect, microfacies modeling technology of multiple iterations and geology tendency under vertical and lateral geology tendency constraint is used. And the attribute models could approximate the real parametric distribution. Moreover, in viewing of the key and potential reservoir sand, the countermeasure on configuration modeling by different stochastic simulation methods and step simulation is proposed to rapidly build geologic models. The geologic models are scientific and feasible. The above-mentioned countermeasures and methods have been used in secondary development of Daqing oilfield and the effect was well. This new technology presents directive sense.

We have been heartened by the response to our article, particularly the letters published above. These emphasise our conclusions, highlight further areas of concern and provide solutions for their management. The term ‘readmission’ is poorly defined.[1][1] Whereas we limited our readmissions to

It is a concern that increasing pressure to diagnose, treat and discharge patients rapidly is leading to unacceptably high readmission rates. Readmissions were studied over a two-month period. Patients were identified through the hospital coding system, and electronic discharge summaries provided details of each admission. In total, 69 readmissions were identified, representing 4.34% of medical admissions. Readmitted patients were older than those with single admissions (median age 75 and 71 years, respectively; p

Ultraviolet photodetector with p-n heterojunction is fabricated by magnetron sputtering deposition of n-type indium gallium zinc oxide (n-IGZO) and p-type nickel oxide (p-NiO) thin films on ITO glass. The performance of the photodetector is largely affected by the conductivity of the p-NiO thin film, which can be controlled by varying the oxygen partial pressure during the deposition of the p-NiO thin film. A highly spectrum-selective ultraviolet photodetector has been achieved with the p-NiO layer with a high conductivity. The results can be explained in terms of the "optically-filtering" function of the NiO layer.

The charge transfer reaction between clotrimazolum and alizarin red was studied spectrophotometrically. The reaction was achieved with good results in water-acetone solution. The apparent molar absorptivity is 8.7 x 10(3) L.mol-1.cm-1 at 525 nm. The Beer's law was obeyed in the range of 0-100 micrograms.mL-1 of clotrimazolum. The composition of the complex is 1:1. The proposed method has been applied successfully to the determination of clotrimazolum tablets.

Anticancer agents interfere with the proliferation and survival of tumor cells by a variety of mechanisms. An important factor in the development of a cytotoxic effect by certain anticancer agents is the localization of drug-induced lesions within the cell nucleus. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by some of these agents. Arsenic trioxide (As2O3) was identified as a very potent anti-leukemic agent by inducing apoptosis. The present study shows that As2O3 significantly inhibits the growth of hepatoblastoma cell line, HepG2, changes the composition of nuclear matrix proteins and reduces the expression of Hsc 70 and HNF4 in HepG2, which in turn initiate a cascade of events that compromise multiple nuclear functions and, ultimately, cell survival.

Sixty gliomas obtained by neurosurgical resections were examined. Paraffin blocks were retrieved from pathological files of the Second Affiliated Hospital in Guangzhou Medical College. The methods of argyrophilic technique for AgNORs staining, and Image Analysis System for measurement of AgNORs were used. Six parameters, which included hcount, count, narea, agnrea, agpern and agperc were used to correlated well with histopathological grades (compared grade 23, grade 34, and grade 24, respectively). We concluded that AgNORs is useful in evaluating proliferative activity and assessing the malignancy of human gliomas. It may also be used as a target for anti-neoplastic drugs in the treatment of gliomas.

To determine whether the sub-Tenon's parabulbar approach for local anesthesia is a safe and effective choice for posterior segment surgery.Prospective, noncomparative case series.Two hundred seventy-six consecutive patients underwent posterior segment surgery at the University of Texas Medical Branch.Two hundred patients received sub-Tenon's parabulbar anesthesia containing an 11 -ml mixture of 5-ml 2% lidocaine (Xylocaine), 5-ml 0.5% bupivacaine (Marcaine), and 1 ml of 150 hyaluronidase (Wydase) units as primary anesthesia. The method did not involve a separate transcutaneous lid nerve or subconjunctival injection.The proportion of cases receiving supplementation (significant intravenous anesthesia, intraoperative local anesthesia, or both) was estimated. Its relationship to duration of surgery and surgical procedures deemed painful was assessed. Surgery lasting 3 hours or more was considered a long duration. Both scleral buckle and cryotherapy were considered painful procedures. The proportion of cases receiving additional local anesthesia preoperatively was also evaluated. Complications associated with sub-Tenon's parabulbar injection were monitored.There were 101 instances of patients receiving additional anesthesia. Nineteen received additional preoperative sub-Tenon's anesthesia, 12 received intraoperative local anesthesia supplementation, and 70 received intravenous medication. Of these 70, 19 required what the authors defined as a significant amount of intravenous medication, three of whom also received intraoperative local anesthesia supplementation. Consequently, 28 of 200 patients (14%; 95% confidence interval: 9.5, 19.6) received supplementation (significant intravenous anesthesia, intraoperative local anesthesia, or both). The proportion of cases receiving supplementation was directly related to duration of surgery. Patients involved in longer cases (51.7% vs. 7.6%; P0.001) and those involved in more painful procedures (48.2% vs. 8.7%; P0.001) were more likely to receive supplementation. Adjusting for surgery duration, a greater proportion of patients undergoing painful procedures required supplementation (31.3% vs. 0.5% for surgery3 hours, P = 0.003; 72.7% vs. 38.9% for surgeryor = 3 hours, P = 0.13). No associated ocular or systemic complications were observed.The results of this large study demonstrate that a single injection of sub-Tenon's anesthesia is relatively safe and effective for achieving local anesthesia during vitrectomies, with or without other intraocular procedures, lasting less than 3 hours. Other types of posterior segment surgery may require supplementation if they are more painful procedures, such as scleral buckle or cryotherapy, or last longer than 3 hours.

1. A combination of store-and-forward technology and videoconferencing technology can be used in eye care and other medical specialties. 2. Bandwidth is a rate-limiting factor for obtaining a high-resolution, real-time image. 3. Protocols, clinical and technical, must be used to implement telemedicine in an efficient and high-quality manner.

The elemental content of anagen hair fibers in a Caucasian population of healthy females and males in the age range 10-69 years was performed to constitute a baseline for further studies of pathological conditions. Proton induced X-ray emission (PIXE) analyses were performed on single hair fibers in triplicate from 103 individuals in order to determine sulfur, zinc, calcium, and chlorine content. The hair fibers were all anagen hairs collected from a site little influenced by genetic and hormonal influences 1.5 cm above the right ear of the probands. An area 5-8 mm from the follicle bottom was chosen for the analysis in all cases to minimize effect of hair-do contamination. The average sulfur content was 0.049 g/g and the average zinc content 170 micrograms/g. These results were not significantly influenced by chloroform/ethanol rinsing before analysis. The calcium and chlorine contents were 330 micrograms/g and 0.0033 g/g respectively. The latter data are expected to be more seriously influenced by external factors (e.g., contamination) than sulfur and zinc. No correlation between elemental concentration and sex was found for sulfur and zinc in the present material. PIXE analysis of single hair fibers yields valuable information on the elemental composition of hair fibers and can be rapidly and efficiently performed after simple mounting procedures.

Content of Zn and Cu in blood and hair and comparative levels of Zn and Cu in blood were determined in 83 patients with aphtosis. Internal and external treatment with Zn preparations in 159 patients with aphtosis produced good results in 81.13% of cases, as evaluated at 1-year follow up review.

In order to study the left ventricular diastolic events in cardiomyopathy, carotid pulse tracing, electrocardiogram, phonocardiogram and apexcardiogram with its first derivatives (dA/dt) were simultaneously recorded in 240 normal subjects, 30 patients with dilated cardiomyopathy (DCM) and 44 patients with hypertrophic cardiomyopathy (HCM). Total relaxation time (TRT), total relaxation time index (TRTI), the ratio of A wave to total diastolic amplitude in apexcardiogram (A/D), diastolic amplitude time index (DATI), the ratio of RF wave in apexcardiogram to the total amplitude of apex tracing (F/H) and the variables reflecting the diastolic properties were measured to evaluate the left ventricular relaxation and compliance. Meanwhile, two variables reflecting the contractile ability of the left ventricle were measured in order to compare with the diastolic events. The results demonstrated that in normal subjects relaxation and compliance of the left ventricle showed a tendency of natural "decay" with aging and in patients with DCM and HCM these were significantly decreased, especially in patients with HCM. A/D, which reflects the left ventricular compliance, was increased in patients with HCM as compared with normal subjects (P less than 0.01) and also with patients with DCM. It means that a greater A/D is in favor of the diagnosis of HCM rather than DCM. In addition to abnormal diastolic events, systolic dysfunction, as evidenced by remarkable abnormalities of the contractile variables (PEP/LVET and R-dA/dt.I), was found as well in patients with DCM.

The estimation of forest biomass is important for practical issues and scientific purposes in forestry. The estimation of forest biomass on a large-scale level would be merely possible with the application of generalized single-tree biomass models. The aboveground biomass data on Masson pine ( Pinus massoniana) from nine provinces in southern China were used to develop generalized single-tree biomass models using both linear mixed model and dummy variable model methods. An allometric function requiring only diameter at breast height was used as a base model for this purpose. The results showed that the aboveground biomass estimates of individual trees with identical diameters were different among the forest origins (natural and planted) and geographic regions (provinces). The linear mixed model with random effect parameters and dummy model with site-specific (local) parameters showed better fit and prediction performance than the population average model. The linear mixed model appears more flexible than the dummy variable model for the construction of generalized single-tree biomass models or compatible biomass models at different scales. The linear mixed model method can also be applied to develop other types of generalized single-tree models such as basal area growth and volume models.