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In this quasi-experimental before-and-after study in a methicillin-resistant staphylococcus aureus (MRSA) high-prevalence acute-care dermatology ward from August 2016 to November 2018, patients admitted during intervention period who received additional topical intranasal octenidine were 63% less likely to acquire MRSA than those receiving universal daily octenidine bathing alone during baseline period (aOR, 0.37; 95% CI, 0.14–0.98).
We propose a novel Fabry–Pérot (FP) antenna consisting of a checkered polarization-conversion metasurface (PCM), corner-cut square patch antennas, and sandwiched compounds. The proposed antenna achieves low radar-cross-section (RCS), high gain, and wideband circular polarization (CP). The corner-cut square patch antennas facilitate high reflectivity, satisfactory transmission magnitude, and the desired phase difference. An embedded metal between two rings of substrate contributes to reducing cross-polarization, improving transmission efficiency, enhancing bandwidth, and reducing RCS. Following simulations, we fabricated a prototype of the proposed antenna and tested its performance. Measurements from the simulation and prototype tests were similar within a reasonable margin of error. Compared with alternative antennas, our proposed FP antenna offers high gain, wideband CP, low cost, a low RCS, and a lower profile.
Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
The classical credibility theory is a cornerstone of experience rating, especially in the field of property and casualty insurance. An obstacle to putting the credibility theory into practice is the conversion of available prior information into a precise choice of crucial hyperparameters. In most real-world applications, the information necessary to justify a precise choice is lacking, so we propose an imprecise credibility estimator that honestly acknowledges the imprecision in the hyperparameter specification. This results in an interval estimator that is doubly robust in the sense that it retains the credibility estimator’s freedom from model specification and fast asymptotic concentration, while simultaneously being insensitive to prior hyperparameter specification.
ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxorubicin (DOX) regimen in the treatment of TNBC. OBJECTIVES/GOALS: The objective of this research project is to develop a novel compound which can activate both 1) the constitutive androstane receptor (CAR) and subsequently enhance the CYP2B6-mediated activation of CPA, and 2) the nuclear factor erythroid- related factor-2 (Nrf2) leading to the cardiomyocyte protection from DOX-associated cardiotoxicity. METHODS/STUDY POPULATION: Following the identification of the compound candidate, DL7076 was evaluated for tissue specific induction of CAR and Nrf2 using qPCR, western blot analysis, and luciferase reporter assays.
Further, we have developed a multicellular coculture model incorporating human primary hepatocytes for metabolism, TNBC spheroids as the target, and cardiomyocytes as a side target of DOX. We have investigated the anticancer effects of CPA/DOX on TNBC cells and the toxic effects on cardiomyocytes with/without a CAR-Nrf2 activator, in a multicellular environment where hepatic metabolism is well-retained. RESULTS/ANTICIPATED RESULTS: We found that our dual activator of CAR and Nrf2, DL7076, exhibits tissue specific induction of CAR and Nrf2. Inclusion of DL7076 in combination with the CPA/DOX regimen improves anticancer efficacy, through the subsequent increase in the formation of the active CPA metabolite. With the addition of DL7076, DOX-mediated off-target cardiotoxicity was markedly reduced.
Lastly, utilizing the novel coculture system with human primary hepatocytes, TNBC spheroids, and cardiomyocytes, the inclusion of DL7076 to the CPA/DOX regimen shows decreased spheroid viability and improved cardiomyocyte viability and function. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that DL7076 can facilitate DOX/CPA containing regimens by increasing CAR-mediated metabolism and subsequent CPA bioactivation while selectively protecting cardiomyocytes from DOX-induced toxicity. This research is expected to translate our basic scientific findings into therapeutic interventions for women with TNBC.
To stop transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in association with myocardial perfusion imaging (MPI) at a cardiology clinic.
Outbreak investigation and quasispecies analysis of HCV hypervariable region 1 genome.
Outpatient cardiology clinic.
Patients undergoing MPI.
Case patients met definitions for HBV or HCV infection. Cases were identified through surveillance registry cross-matching against clinic records and serological screening. Observations of clinic practices were performed.
During 2012–2014, 7 cases of HCV and 4 cases of HBV occurred in 4 distinct clusters among patients at a cardiology clinic. Among 3 case patients with HCV infection who had MPI on June 25, 2014, 2 had 98.48% genetic identity of HCV RNA. Among 4 case patients with HCV infection who had MPI on March 13, 2014, 3 had 96.96%–99.24% molecular identity of HCV RNA. Also, 2 clusters of 2 patients each with HBV infection had MPI on March 7, 2012, and December 4, 2014. Clinic staff reused saline vials for >1 patient. No infection control breaches were identified at the compounding pharmacy that supplied the clinic. Patients seen in clinic through March 27, 2015, were encouraged to seek testing for HBV, HCV, and human immunodeficiency virus. The clinic switched to all single-dose medications and single-use intravenous flushes on March 27, 2015, and no further cases were identified.
This prolonged healthcare-associated outbreak of HBV and HCV was most likely related to breaches in injection safety. Providers should follow injection safety guidelines in all practice settings.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
In order to maximize the utility of future studies of trilobite ontogeny, we propose a set of standard practices that relate to the collection, nomenclature, description, depiction, and interpretation of ontogenetic series inferred from articulated specimens belonging to individual species. In some cases, these suggestions may also apply to ontogenetic studies of other fossilized taxa.
A series of new synthetic armored cables were developed and tested to ensure that they were suitable for use with the RECoverable Autonomous Sonde (RECAS), which is a newly designed freezing-in thermal ice probe. The final version of the cable consists of two concentric conductors that can be used as the power and signal lines. Two polyfluoroalkoxy jackets are used for electrical insulation (one for insulation between conductors, and the other for insulation of the outer conductor). The outer insulation layer is coated by polyurethane jacket to seal the connections between the cable and electrical units. The 0.65 mm thick strength member is made from aramid fibers woven together. To hold these aramid fibers in place, a sheathing layer was produced from a polyamide fabric cover net. The outer diameter of the final version of the cable is ~6.1 mm. The permissible bending radius is as low as 17–20 mm. The maximal breaking force under straight tension is ~12.2 kN. The cable weight is only ~0.061 kg m−1. The mechanical and electrical properties and environmental suitability of the cable were determined through laboratory testing and joint testing with the probe.
For a wide range of insect species, the microbiota has potential roles in determining host developmental programme, immunity and reproductive biology. The tea geometrid moths Ectropis obliqua and E. grisescens are two closely related species that mainly feed on tea leaves. Although they can mate, infertile hybrids are produced. Therefore, these species provide a pair of model species for studying the molecular mechanisms of microbiotal involvement in host reproductive biology. In this study, we first identified and compared the compositions of microbiota between these sibling species, revealing higher microbiotal diversity for E. grisescens. The microbiota of E. obliqua mainly comprised the phyla Firmicutes, Proteobacteria and Cyanobacteria, whereas that of E. grisescens was dominated by Proteobacteria, Actinobacteria and Firmicutes. At the genus level, the dominant microbiota of E. grisescens included Wolbachia, Enterobacter and Pseudomonas and that of E. obliqua included Melissococcus, Staphylococcus and Enterobacter. Furthermore, we verified the rate of Wolbachia to infect 80 samples from eight different geographical populations, and the results supported that only E. grisescens harboured Wolbachia. Taken together, our findings indicate significantly different microbiotal compositions for E. obliqua and E. grisescens, with Wolbachia possibly being a curial factor influencing the reproductive isolation of these species. This study provides new insight into the mechanisms by which endosymbiotic bacteria, particularly Wolbachia, interact with sibling species.
From 21 January 2020 to 9 February 2020, three family clusters involving 31 patients with coronavirus disease 2019 were identified in Wenzhou, China. The epidemiological and clinical characteristics of the family cluster patients were analysed and compared with those of 43 contemporaneous sporadic cases. The three index cases transmitted the infection to 28 family members 2–10 days before illness onset. Overall, 28 of the 41 sporadic cases and three of 31 patients in the family clusters came back from Wuhan (65.12 vs. 9.68%, P< 0.001). In terms of epidemiological characters and clinical symptoms, no significant differences were observed between the family cluster and sporadic cases. However, the lymphocyte counts of sporadic cases were significantly lower than those of family cluster cases ((1.32 ± 0.55) × 109/l vs. (1.63 ± 0.70) × 109/l, P = 0.037), and the proportion of hypoalbuminaemia was higher in sporadic cases (18/43, 41.86%) than in the family clusters (6/31, 19.35%) (P < 0.05). Within the family cluster, the second- and third-generation cases had milder clinical manifestations, without severe conditions, compared with the index and first-generation cases, indicating that the virulence gradually decreased following passage through generations within the family clusters. Close surveillance, timely recognition and isolation of the suspected or latent patient is crucial in preventing family cluster infection.
To alert policy makers early about emerging health technologies that could significantly impact the healthcare system at the clinical, financial and organizational levels, the Agency for Care Effectiveness (ACE) in Singapore established a horizon scanning system (HSS) in 2019. This paper describes the development of the ACE HSS and showcases its application with cell and gene therapy products as the first example.
A literature review of existing HSS methods, including the processes of the EuroScan International Network and other overseas horizon scanning agencies, was done to inform the development of our horizon scanning framework. The framework was first applied to the new and emerging cell and gene therapies.
Identification sources, filtration and prioritization criteria, and horizon scanning outputs for the HSS were developed in alignment to international best practices, with recommendations for technology uptake represented by a traffic light system. For the first horizon scanning exercise on cell and gene therapies, forty therapies passed the filtration step, of which eight were prioritized for further assessment. The few early reports developed were used to inform and prepare the healthcare system for their potential introduction, particularly in terms of the need to develop health and funding policies.
Early assessment of prioritized topics has provided support for strategic efforts within the Ministry of Health. Given that ACE's horizon scanning program is still in its infancy, the framework will continue to evolve to ensure relevance to our stakeholders so that it remains fit for purpose for our healthcare system.
The Wulanba granite, consisting of biotite monzogranite and syenogranite, is located in the southern part of the Great Xing’an Range, NE China. Whole-rock major- and trace-element geochemistry suggests the Wulanba granite is a high-K–shoshonitic, slightly peraluminous and highly differentiated I-type granite. The Sr–Nd–Hf isotopes indicate that it originated from partial melting of juvenile crust derived from the depleted mantle with a minor input of old crust. The relatively young T2DM and tDM2 ages indicate it was most likely derived from a Late Neoproterozoic to Early Palaeozoic source. We have demonstrated that the biotite monzogranite is the ore-related intrusion of the Haobugao Zn–Fe mineralization based on the following geological, geochronological and geochemical evidence: (1) the chalcopyrite/pyrite in the biotite monzogranite and the continuous mineralization of drill core ZK2508; (2) the consistence of the emplacement age of the biotite monzogranite (~141–140/138 Ma) with the skarn mineralization age (~142 Ma); and (3) the presence of rich ore-forming elements (Fe–Zn–Cu) in the biotite monzogranite, and the similar Pb compositions of the sulfides from the Haobugao deposit and the biotite monzogranite. Compared to the barren syenogranite, the fertile biotite monzogranite is more oxidized, while the edges of the apatite grains in the biotite monzogranite are more oxidized than the centres. The average F/Cl ratio of the fertile biotite monzogranite (~123.45) is much higher than that of the barren syenogranite (~73.98). We conclude that these differences reflect unique geochemical signatures, and the geochemical composition of the apatite can be used to infer the economic potential of granites.
A 15-year-old teenager presented with a 2-month history of headache. Neurological examination was normal except for papilledema. Further lumbar puncture indicated intracranial hypertension (330 mm H2O). Brain magnetic resonance imaging (MRI) was normal but phase contrast-magnetic resonance venography (PC-MRV) (Figure 1(A)) suggested possible left transverse-sigmoid sinus thrombosis; subsequent contrast-enhanced 3D fat-saturated T1 volumetric isotropic turbo spin echo acquisition (VISTA) MRI (Figure 1(B)) confirmed the pathology. Hyper-coagulable panel results (including six steroid sex hormones, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies) were all within normal range. In further examination, computed tomography (CT) venography images (Figure 1(C) and (D)) showed that the left jugular vein was compressed by the styloid process, consistent with Eagle syndrome.1 The patient who refused the recommended surgical treatment, however, chose anticoagulant therapy consisting of low-molecular weight heparin subcutaneous injection in addition to new oral anticoagulant. At 18-month follow-up, the patient reported no symptoms remained.
As distinctive spontaneous polarization and far-infrared radiation characteristics, the natural mineral tourmaline (TM) has the regulatory effect on crystallization behavior, which possesses potential application in biomimetic mineralization and bone regeneration. In this study, polyurethane (PU) and gelatin (GE) membranes with different adding proportion of TM nanoparticles were prepared via electrospinning. Additionally, the effect of TM nanoparticles on the mineralization process of hydrophobic PU and hydrophilic GE was investigated by immersing the composite TM/PU and TM/GE electrospun membranes in the 10× simulated body fluid (10SBF) at 37 °C for varying periods of time. SEM images confirmed the well-dispersed TM nanoparticles in the PU and GE electrospun fibers. The mineralization deposition was characterized by the SEM, EDS, XRD, and FTIR, and it indicated that two types of calcium phosphate deposits with different Ca/P molar ratios were obtained when TM/PU membranes and TM/GE membranes were incubated in 10SBF. Honeycomb-like hydroxyapatite crystals nucleated and grew faster on TM/PU and TM/GE membranes than the pure PU and GE membranes, respectively. Furthermore, with the increase of the added TM nanoparticles in the composite membranes, more calcium phosphate crystals were precipitated. These results showed that the added TM nanoparticles were able to improve the mineralization of polymer fibrous membranes, which is potential for the composite bone scaffold.
Direct determination of barrier height (ΦBH) value between Ir and single crystal (001) hydrogen-terminated diamond with lightly boron doped has been performed using x-ray photoelectron spectroscopy technique. 70 nm Ir islands were formed on hydrogen-terminated diamond surface using anodic aluminum oxide. The ΦBH value for Ir/hydrogen-terminated diamond was −0.43 ± 0.14 eV, indicating that Ir was a suitable metal for ohmic contact with hydrogen-terminated diamond. The band diagram of Ir/hydrogen-terminated diamond was obtained. The experimental ΦBH was compared with the theoretical ΦBH in this work.
Research suggests that cause lawyers are a diverse group. Death penalty lawyers with attachment to political institutions and a strong commitment to procedurals tend to have a unique path to professional identification, participation in the legal process and acquiring the ability to affect case outcomes. Borrowing from Hilbink's typologies and Liu and Halliday's analytical framework, this study examines in detail the practices of proceduralist and progressive elite lawyers. It uses a high-profile capital case, the Nian Bin case, as a case study to analyse the motivation and strategies of the lead defence lawyer in the context of progressive proceduralist cause lawyers. Relevant theoretical and policy implications as well as suggestions for future studies are discussed.
Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD.
A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed.
In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27–34%], 1-year prevalence was 8% (95% CI 3–14%) and 1-month prevalence was 24% (95% CI 15–34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting.
This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.
The following paper investigates the prevalence and characteristics of asymptomatic norovirus infection in the population living around oyster farm sites. Two consecutive surveys were conducted from January 2014 to December 2014 and 4549 stool samples were screened during the same time period. The total asymptomatic infection rate was 4.04% (184/4549). Norovirus infection rate was 5.20% in oyster farming population which was significantly higher compared with non-farming population where the infection rate was 3.65% (χ2 = 5.49, P < 0.05). A total of 184 NoV positive samples were identified by real time-quantitative polymerase chain reaction (RT-qPCR) and semi-nested RT-PCR and 136 sequences were obtained. The sequences were clustered into 14 genotypes. GI strains were clustered into six genotypes, including GI.2, GI.3, GI.5, GI.6, GI.8 and GI.9; while GII strains were clustered into GII.2, GII.3, GII.4, GII.5, GII.6, GII.8 and GII.13. GI.9 and GII.17 were the predominant and most prevalent genotypes, respectively. The GII.17 genotype replaced GII.4 becoming the dominant genotype in the oyster farming area in 2014. To sum up, long-term monitoring of asymptomatic infection is crucial for the detection of new variant strains and for identifying outbreaks during the early stage.