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Fricative consonants are known to be pronounced by controlling turbulent flow inside a vocal tract. In this study, a simplified vocal tract model was proposed to investigate the characteristics of flow and sound during production of the fricative [s] in a word context. By controlling the inlet flow rate and tongue speed, the acoustic characteristics of [s] were reproduced by the model. The measurements with a microphone and a hot-wire anemometer showed that the flow velocity at the teeth gap and far-field sound pressure started oscillating before the tongue reached the /s/ position, and continued during tongue descent. This behaviour was not affected by the changes of the tongue speed. These results indicate that there is a time shift between source generation and tongue movement. This time shift can be a physical constraint in the articulation of words which include /s/. With the proposed model, we could investigate the effects of tongue speed on the flow and sound generation in a parametric way. The proposed methodology is applicable for other phonemes to further explore the aeroacoustics of phonation. [ABSTRACT FROM AUTHOR]

Studies conducted in time series could be far more informative than those that only capture a specific moment in time. However, when it comes to transcriptomic data, time points are sparse creating the need for a constant search for methods capable of extracting information out of experiments of this kind. We propose a feature selection algorithm embedded in a hidden Markov model applied to gene expression time course data on either single or even multiple biological conditions. For the latter, in a simple case-control study features or genes are selected under the assumption of no change over time for the control samples, while the case group must have at least one change. The proposed model reduces the feature space according to a two-state hidden Markov model. The two states define change/no-change in gene expression. Features are ranked in consonance with three scores: number of changes across time, magnitude of such changes and quality of replicates as a measure of how much they deviate from the mean. An important highlight is that this strategy overcomes the few samples limitation, common in transcriptome experiments through a process of data transformation and rearrangement. To prove this method, our strategy was applied to three publicly available data sets. Results show that feature domain is reduced by up to 90% leaving only few but relevant features yet with findings consistent to those previously reported. Moreover, our strategy proved to be robust, stable and working on studies where sample size is an issue otherwise. Hence, even with two biological replicates and/or three time points our method proves to work well. [ABSTRACT FROM AUTHOR]

We study the relationship between the performance of firms and their technological portfolios using tools borrowed from complexity science. In particular, we ask whether the accumulation of knowledge and capabilities associated with a coherent set of technologies leads firms to experience advantages in terms of productive efficiency. To this end, we analyze both the balance sheets and the patenting activity of about 70 thousand firms that have filed at least one patent over the period 2004-2013. We define a measure of corporate coherent diversification, based on the bipartite network linking companies with the technological fields in which they patent, and relate it to firm performance in terms of labor productivity. Our measure favors technological portfolios that can be decomposed into large blocks of closely related fields over portfolios with the same breadth of scope, but a more scattered diversification structure. We find that the coherent diversification of firms is quantitatively related with their economic performance and captures relevant information about their productive structure. In particular, we prove on a statistical basis that a naive definition of technological diversification can explain labor productivity only as a proxy of size and coherent diversification. This approach can be used to investigate possible synergies within firms and to recommend viable partners for mergers and acquisitions. [ABSTRACT FROM AUTHOR]

Mutualistic plant-microbe associations are widespread in natural ecosystems and have made major contributions throughout the evolutionary history of terrestrial plants. Amongst the most remarkable of these are the so-called root endosymbioses, resulting from the intracellular colonization of host tissues by either arbuscular mycorrhizal (AM) fungi or nitrogen-fixing bacteria that both provide key nutrients to the host in exchange for energy-rich photosynthates. Actinorhizal host plants, members of the Eurosid 1 clade, are able to associate with both AM fungi and nitrogen-fixing actinomycetes known as Frankia. Currently, little is known about the molecular signaling that allows these plants to recognize their fungal and bacterial partners. In this article, we describe the use of an in vivo Ca2+ reporter to identify symbiotic signaling responses to AM fungi in roots of both Casuarina glauca and Discaria trinervis, actinorhizal species with contrasting modes of Frankia colonization. This approach has revealed that, for both actinorhizal hosts, the short-chain chitin oligomer chitotetraose is able to mimic AM fungal exudates in activating the conserved symbiosis signaling pathway (CSSP) in epidermal root cells targeted by AM fungi. These results mirror findings in other AM host plants including legumes and the monocot rice. In addition, we show that chitotetraose is a more efficient elicitor of CSSP activation compared to AM fungal lipo-chitooligosaccharides. These findings reinforce the likely role of short-chain chitin oligomers during the initial stages of the AM association, and are discussed in relation to both our current knowledge about molecular signaling during Frankia recognition as well as the different microsymbiont root colonization mechanisms employed by actinorhizal hosts. [ABSTRACT FROM AUTHOR]

In single molecule fluorescence studies, background emission from labeled substrates often restricts their concentrations to non-physiological nanomolar values. One approach to address this challenge is the use of zero-mode waveguides (ZMWs), nanoscale holes in a thin metal film that physically and optically confine the observation volume allowing much higher concentrations of fluorescent substrates. Standard fabrication of ZMWs utilizes slow and costly E-beam nano-lithography. Herein, ZMWs are made using a self-assembled mask of polystyrene microspheres, enabling fabrication of thousands of ZMWs in parallel without sophisticated equipment. Polystyrene 1 μm dia. microbeads self-assemble on a glass slide into a hexagonal array, forming a mask for the deposition of metallic posts in the inter-bead interstices. The width of those interstices (and subsequent posts) is adjusted within 100–300 nm by partially fusing the beads at the polystyrene glass transition temperature. The beads are dissolved in toluene, aluminum or gold cladding is deposited around the posts, and those are dissolved, leaving behind an array ZMWs. Parameter optimization and the performance of the ZMWs are presented. By using colloidal self-assembly, typical laboratories can make use of sub-wavelength ZMW technology avoiding the availability and expense of sophisticated clean-room environments and equipment. [ABSTRACT FROM AUTHOR]

Background: Pancreatic islets are heavily vascularized in vivo yet lose this vasculature after only a few days in culture. Determining how to maintain islet vascularity in culture could lead to better outcomes in transplanting this tissue for the treatment of type 1 diabetes as well as provide insight into the complex communication between beta-cells and endothelial cells (ECs). We previously showed that islet ECs die in part due to limited diffusion of serum albumin into the tissue. We now aim to determine the impact of hypoxia on islet vascularization. Methods: We induced hypoxia in cultured mouse islets using the hypoxia mimetic cobalt chloride (100 μM CoCl2). We measured the impact on islet metabolism (two-photon NAD(P)H and Rh123 imaging) and function (insulin secretion and survival). We also measured the impact on hypoxia related transcripts (HIF-1α, VEGF-A, PDK-1, LDHA, COX4) and confirmed increased VEGF-A expression and secretion. Finally, we measured the vascularization of islets in static and flowing culture using PECAM-1 immunofluorescence. Results: CoCl2 did not induce significant changes in beta cell metabolism (NAD(P)H and Rh123), insulin secretion, and survival. Consistent with hypoxia induction, CoCl2 stimulated HIF-1α, PDK-1, and LDHA transcripts and also stimulated VEGF expression and secretion. We observed a modest switch to the less oxidative isoform of COX4 (isoform 1 to 2) and this switch was noted in the glucose-stimulated cytoplasmic NAD(P)H responses. EC morphology and survival were greater in CoCl2 treated islets compared to exogenous VEGF-A in both static (dish) and microfluidic flow culture. Conclusions: Hypoxia induction using CoCl2 had a positive effect on islet EC morphology and survival with limited impact on beta-cell metabolism, function, and survival. The EC response appears to be due to endogenous production and secretion of angiogenic factors (e.g. VEGF-A), and mechanistically independent from survival induced by serum albumin. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis C virus (HCV) causes both acute and chronic infection, which can potentially develop into cirrhosis and liver cancer. Healthcare systems are struggling to finance costly direct-acting antiviral agents through public funding for uninsured patients, despite the unprecedented high cure rates of these agents. Vulnerable populations are at higher risk of HCV infection. The personal importation scheme is based on the legal right to import any unauthorized generics for personal use. This study was designed to assess the knowledge and perceptions of stakeholders on unauthorized generics. Methods: We conducted an anonymous online survey based on the fictitious situation of a patient diagnosed with HCV who lacked mandatory health insurance and personal financial resources. Results: We obtained a sample of 781 respondents: 445 physicians, 77 pharmacists, 51 patients and 207 non-healthcare professionals. We found that only 36% and 58% of respondents believe that the quality and efficacy, respectively, of unauthorized generics are equivalent to their corresponding brand. An overwhelming majority (98%) favoured quality control upon arrival, and 31% felt they could recognize fraudulent websites. A total of 79% expressed support for financial assistance for vulnerable patients, and support among physicians was 83%. Conclusions: Overall, the limited knowledge of the efficacy and quality of unauthorized generics, despite evidence in peer-reviewed literature, contrasts with the overwhelmingly positive attitudes toward financial assistance for personal import. This finding emphasizes the need for clearer information on imported generics and the potential safety provided by buyers' club schemes to complete the WHO agenda of eradicating viral hepatitis by 2030 within otherwise excluded vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate. Method: We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance. Results: A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time. Conclusion: The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care. [ABSTRACT FROM AUTHOR]

To enrich any model and its dynamics introduction of delay is useful, that models a precise description of real-life phenomena. Differential equations in which current time derivatives count on the solution and its derivatives at a prior time are known as delay differential equations (DDEs). In this study, we are introducing new techniques for finding the numerical solution of fractional delay differential equations (FDDEs) based on the application of neural minimization (NM) by utilizing Chebyshev simulated annealing neural network (ChSANN) and Legendre simulated annealing neural network (LSANN). The main purpose of using Chebyshev and Legendre polynomials, along with simulated annealing (SA), is to reduce mean square error (MSE) that leads to more accurate numerical approximations. This study provides the application of ChSANN and LSANN for solving DDEs and FDDEs. Proposed schemes can be effortlessly executed by using Mathematica or MATLAB software to get explicit solutions. Computational outcomes are depicted, for various numerical experiments, numerically and graphically with error analysis to demonstrate the accuracy and efficiency of the methods. [ABSTRACT FROM AUTHOR]

For early breast cancer detection, mammography is nowadays the commonly used standard imaging approach, offering a valuable clinical tool for visualization of suspicious findings like microcalcifications and tumors within the breast. However, due to the superposition of anatomical structures, the sensitivity of mammography screening is limited. Within the last couple of years, the implementation of contrast-enhanced spectral mammography (CESM) based on K-edge subtraction (KES) imaging helped to improve the identification and classification of uncertain findings. In this study, we introduce another approach for CESM based on a two-material decomposition, with which we expect fundamental improvements compared to the clinical procedure. We demonstrate the potential of our proposed method using the quasi-monochromatic radiation of a compact synchrotron source—the Munich Compact Light Source (MuCLS)—and a modified mammographic accreditation phantom. For direct comparison with the clinical CESM approach, we also performed a standard dual-energy KES at the MuCLS, which outperformed the clinical CESM images in terms of contrast-to-noise ratio (CNR) and spatial resolution. However, the dual-energy-based two-material decomposition approach achieved even higher CNR values. Our experimental results with quasi-monochromatic radiation show a significant improvement of the image quality at lower mean glandular dose (MGD) than the clinical CESM. At the same time, our study indicates the great potential for the material-decomposition instead of clinically used KES to improve the quantitative outcome of CESM. [ABSTRACT FROM AUTHOR]

Objectives: To investigate effects of postural changes and bladder distention on intrabladder pressure whilst estimating intra-abdominal pressure in horses. Design: Two-year cohort study. Patients admitted for elective surgical procedures unrelated to gastrointestinal or genitourinary tract. Setting: School of Agricultural and Veterinarian Sciences, Jaboticabal, SP, Brazil. Animals: 20 adult horses, 11 males (stallions and geldings) and 9 females; between 3.5 and 12 years, weighing 350 to 500 kg. Interventions: Intra-abdominal pressure was directly-recorded through abdominocentesis at the ventral midline with a fluid-filled system. Intrabladder pressure was obtained from a bladder catheter with the fluid-filled system zeroed at the level of the tuber ischia with patients in dorsal recumbency or pubic symphysis if in lateral recumbency. Measurements and main results: Body position directly influenced intra-abdominal pressure. In dorsal recumbency, intra-abdominal pressure differed (p < 0.05) from intrabladder pressure at end-inspiration and end-expiration regardless of whether the bladder was empty or distended. There was no correlation nor association between the two pressures in this body position. In lateral recumbency a difference (p <0.05) between intra-abdominal pressure and intrabladder pressure was recorded at end-inspiration with the bladder distended with 25 ml, and at end-expiration for distension volumes of 25 ml and 50 ml. There was a strong correlation between both pressures for left and right lateral recumbency, regardless of the distension volume. Ordinary least product (OLP) regression analysis showed no fixed or proportional bias between both pressures for distension volume of 50 ml, at both end-inspiration and end-expiration. Conclusions: Indirect assessment of equine intra-abdominal pressure cannot be made in dorsal recumbency. For that purpose, patients should be in left lateral recumbency with the bladder distended with 50 ml. Values can be recorded at end-inspiration or end-expiration. Restriction: Occlusion of the catheter tip by the bladder wall when minimally distended. [ABSTRACT FROM AUTHOR]

The development of automatic methods for segmenting anatomy from medical images is an important goal for many medical and healthcare research areas. Datasets that can be used to train and test computer algorithms, however, are often small due to the difficulties in obtaining experts to segment enough examples. Citizen science provides a potential solution to this problem but the feasibility of using the public to identify and segment anatomy in a medical image has not been investigated. Our study therefore aimed to explore the feasibility, in terms of performance and motivation, of using citizens for such purposes. Public involvement was woven into the study design and evaluation. Twenty-nine citizens were recruited and, after brief training, asked to segment the spine from a dataset of 150 magnetic resonance images. Participants segmented as many images as they could within three one-hour sessions. Their accuracy was evaluated by comparing them, as individuals and as a combined consensus, to the segmentations of three experts. Questionnaires and a focus group were used to determine the citizens' motivation for taking part and their experience of the study. Citizen segmentation accuracy, in terms of agreement with the expert consensus segmentation, varied considerably between individual citizens. The citizen consensus, however, was close to the expert consensus, indicating that when pooled, citizens may be able to replace or supplement experts for generating large image datasets. Personal interest and a desire to help were the two most common reasons for taking part in the study. [ABSTRACT FROM AUTHOR]

A fundamental question regarding music processing is its degree of independence from speech processing, in terms of their underlying neuroanatomy and influence of cognitive traits and abilities. Although a straight answer to that question is still lacking, a large number of studies have described where in the brain and in which contexts (tasks, stimuli, populations) this independence is, or is not, observed. We examined the independence between music and speech processing using functional magnetic resonance imagining and a stimulation paradigm with different human vocal sounds produced by the same voice. The stimuli were grouped as Speech (spoken sentences), Hum (hummed melodies), and Song (sung sentences); the sentences used in Speech and Song categories were the same, as well as the melodies used in the two musical categories. Each category had a scrambled counterpart which allowed us to render speech and melody unintelligible, while preserving global amplitude and frequency characteristics. Finally, we included a group of musicians to evaluate the influence of musical expertise. Similar global patterns of cortical activity were related to all sound categories compared to baseline, but important differences were evident. Regions more sensitive to musical sounds were located bilaterally in the anterior and posterior superior temporal gyrus (planum polare and temporale), the right supplementary and premotor areas, and the inferior frontal gyrus. However, only temporal areas and supplementary motor cortex remained music-selective after subtracting brain activity related to the scrambled stimuli. Speech-selective regions mainly affected by intelligibility of the stimuli were observed on the left pars opecularis and the anterior portion of the medial temporal gyrus. We did not find differences between musicians and non-musicians Our results confirmed music-selective cortical regions in associative cortices, independent of previous musical training. [ABSTRACT FROM AUTHOR]

Introduction: Videolaryngoscopy (VL) as a new airway management technique has evolved in recent decades, and a large number of videolaryngoscopes are now available on the market. Most recent major guidelines already recommend the immediate availability and use of VL in difficult airway management scenarios. However, national data on the availability of VL, introduction into practice and patterns of use are rarely published. Therefore, the current study aimed to provide data on VL in Hungary. Materials and methods: An electronic survey was designed and popularized with the help of the Hungarian Society of Anaesthesiology and Intensive Therapy to explore the availability, use, and practice of and attitudes toward VL among Hungarian anesthesiologists. The survey was conducted between 01.01.2018 and 31.12.2018. Results: In total, 324 duly completed forms were returned and analyzed. Responders were mainly males (58%), specialists (80%) and those involved mainly in anesthesia practice (68%) in the public sector. Two hundred and ten (65%) responders had access to various videolaryngoscopes and were mainly from surgery, intensive care and traumatology units. No responders reported the availability of eight videolaryngoscopes out of the eighteen listed devices, and 32% of the responders had never used any videolaryngoscope in clinical settings. The most commonly available devices were KingVision, MacGrath Mac and Airtraq. Most of the responders reported using videolaryngoscopes mainly for difficult airway management and reported using a fiberscope as the first alternative device. Popular methods for selecting videolaryngoscopes included the following: short clinical trial (n = 67/324), decision of the departmental lead (n = 65/324) and price (n = 54/324). The majority of responders had some training prior to clinical application, but training was mainly voluntary. Overall, 98% of the responders considered videolaryngoscopes beneficial. Conclusions: Approximately two-thirds of Hungarian anesthesiologists have immediate access to videolaryngoscopes, which are used mainly for difficult airway management. The overall attitude towards VL is positive, and many videolaryngoscopes are known and have been used by Hungarian anesthesiologists. However, only a few devices on the market are used commonly. Based on the results, further improvement might be recommended regarding VL training and availability. [ABSTRACT FROM AUTHOR]

The neural representation and perceptual salience of tonal signals presented in different noise maskers were investigated. The properties of the maskers and signals were varied such that they produced different amounts of either monaural masking release, binaural masking release, or a combination of both. The signals were then presented at different levels above their corresponding masked thresholds and auditory evoked potentials (AEPs) were measured. It was found that, independent of the masking condition, the amplitude of the P2 component of the AEP was similar for the same stimulus levels above masked threshold, suggesting that both monaural and binaural effects of masking release were represented at the level of the auditory pathway where P2 is generated. The perceptual salience of the signal was evaluated at equal levels above masked threshold using a rating task. In contrast to the electrophysiological findings, the subjective ratings of the perceptual signal salience were less consistent with the signal level above masked threshold and varied strongly across listeners and masking conditions. Overall, the results from the present study suggest that the P2 amplitude of the AEP represents an objective indicator of the audibility of a target signal in the presence of complex acoustic maskers. [ABSTRACT FROM AUTHOR]

The developmental speed of new antimicrobials does not meet the emergence of multidrug-resistant bacteria sufficiently. A potential shortcut is assessing the antimicrobial activity of already approved drugs. Intrudingly, the antibacterial action of glatiramer acetate (GA) has recently been discovered. GA is a well-known and safe immunomodulatory drug particular effective against Gram-negative bacteria, which disrupts biological membranes by resembling the activity of antimicrobial peptides. Thus, GA can potentially be included in treatment strategies used to combat infections caused by multidrug-resistant Gram-negatives. One potential application is chronic respiratory infections caused by Pseudomonas aeruginosa, however the safety of GA inhalation has never been assessed. Here, the safety of inhaling nebulized GA is evaluated in a preclinical pig model. The potential side effects, i.e., bronchoconstriction, respiratory tract symptoms and systemic- and local inflammation were assessed by ventilator monitoring, clinical observation, biochemistry, flowcytometry, and histopathology. No signs of bronchoconstriction assessed by increased airway peak pressure, Ppeak, or decreased oxygen pressure were observed. Also, there were no signs of local inflammation in the final histopathology examination of the pulmonary tissue. As we did not observe any potential pulmonary side effects of inhaled GA, our preliminary results suggest that GA inhalation is safe and potentially can be a part of the treatment strategy targeting chronic lung infections caused by multidrug-resistant Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted actin-related protein 2/3 (Arp2/3) and the WASP-family verprolin homologous protein (WAVE) complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments. [ABSTRACT FROM AUTHOR]

We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects in Lima, Peru that conducted under an approved study protocol in Peru. The sera were made anonymous under a protocol approved by the CDC Institutional Review Board. Definitive diagnosis of the specimen was established by computed-tomography and/or magnetic resonance imaging. To test the specificity of the assay, we evaluated a panel of serum samples obtained from patients with other infections (n = 24), and serum samples from persons in the United States and Egypt who had not traveled outside their country, and therefore are presumed negative for cysticercosis (n = 128). The assay specificity in the negative panel was 99% (95–100%) while assay sensitivity was 89% (79–95%) in NCC patients with two or more viable cysts. Our assay has performance characteristics similar to those of traditional platforms for the detection of NCC and shows promise as a mobile phone reader-based point-of-care test for antibody detection. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the changes in the demographic, clinical, and biometric characteristics of APAC patients in South Korea during the last decade. Methods: Medical records of patients with APAC who visit the emergency department or the glaucoma clinic of Chonnam National University Hospital, a tertiary referral center in Gwangju, South Korea in 2007 and 2017 were analyzed. Demographics, clinical characteristics, and treatment modality were compared between the APAC patients in 2007 and 2017. Results: The number of patients with APAC increased from 54 in 2007 to 68 in 2017. Female patients in their 60s were most common in both groups and there was no significant difference in IOP, cataract grade, gonioscopic grading, PAS, or optic nerve damage between the two groups at baseline visit (all P > 0.05). However, APAC eyes in 2017 had a shallower ACD (1.74 ± 0.28 mm vs 1.87 ± 0.35 mm; P = 0.024) and greater LV (1.05 ± 0.26 mm vs 0.93 ± 0.19 mm; P = 0.001) than those of APAC eyes in 2007. During one year follow-up, 25 patients (51.02%) received LPI only, and 18 patients (36.73%) required LE, and 6 patients (12.24%) required phacotrabeculectomy or sequential LE and trabeculectomy. However, in 2017, LPI alone was sufficient in 23 patients (38.33%), 29 patients (48.33%) required further LE, and 8 patients (13.33%) required phacotrabeculectomy or sequential LE and trabeculectomy for the treatment of APAC (P = 0.015). Conclusions: Compared to older cases of APAC, recent cases received LE more frequently, which suggests an increasing trend of LE as a treatment option for APAC. In addition, recent cases had a greater LV and shallower ACD than older cases and these biometric differences may be one of the reasons for increasing rate of LE in this study. [ABSTRACT FROM AUTHOR]

The question of how self-driving cars should behave in dilemma situations has recently attracted a lot of attention in science, media and society. A growing number of publications amass insight into the factors underlying the choices we make in such situations, often using forced-choice paradigms closely linked to the trolley dilemma. The methodology used to address these questions, however, varies widely between studies, ranging from fully immersive virtual reality settings to completely text-based surveys. In this paper we compare virtual reality and text-based assessments, analyzing the effect that different factors in the methodology have on decisions and emotional response of participants. We present two studies, comparing a total of six different conditions varying across three dimensions: The level of abstraction, the use of virtual reality, and time-constraints. Our results show that the moral decisions made in this context are not strongly influenced by the assessment, and the compared methods ultimately appear to measure very similar constructs. Furthermore, we add to the pool of evidence on the underlying factors of moral judgment in traffic dilemmas, both in terms of general preferences, i.e., features of the particular situation and potential victims, as well as in terms of individual differences between participants, such as their age and gender. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective decisional analysis study is to develop the prediction model of suicidal ideation. We used a Decision Tree Analysis using SPSS 23.0 program to explore predictors of suicide thoughts for 12,015 Korean adults aged 19–98 years. As a result, the most powerful predictor of suicidal ideation was the level of depression. Of people who suspected depression (CESD-11>16), 32.6% experienced suicidal ideation, which is 12 times higher than that of total subjects. The group with the highest rate of suicidal ideation was people who experienced financial difficulties in depression-suspected group and the rate of suicidal thoughts in this group was 56.7%, which was the highest rate. However, in the non-depressive group, the satisfaction of family relationship was the strongest predictor of suicidal ideation. In the non-depressive group, the rate of suicidal thoughts of people with high level of family relationship satisfaction and high level of health satisfaction was 0.6%, which was the lowest rate. The contribution of this study was that it provided the combination of variables to predict the risk groups of adult suicide. This study suggests that researchers and clinicians should consider comprehensively depressive symptoms, family relationships, economic difficulties, and health status to prevent the suicide of adults. [ABSTRACT FROM AUTHOR]

In nature, protozoa play a major role in controlling bacterial populations. This paper proposes a microfluidic device for the study of protozoa behaviors change due to their chemotactic response in the presence of bacterial cells. A three-channel microfluidic device was designed using a nitrocellulose membrane into which channels were cut using a laser cutter. The membrane was sandwiched between two glass slides; a Euglena suspension was then allowed to flow through the central channel. The two side channels were filled with either, 0.1% peptone as a negative control, or a Listeria suspension respectively. The membrane design prevented direct interaction but allowed Euglena cells to detect Listeria cells as secretions diffused through the nitrocellulose membrane. A significant number of Euglena cells migrated toward the chambers near the bacterial cells, indicating a positive chemotactic response of Euglena toward chemical cues released from Listeria cells. Filtrates collected from Listeria suspension with a series of molecular weight cutoffs (3k, 10k and 100k) were examined in Euglena chemotaxis tests. Euglena cells were attracted to all filtrates collected from the membrane filtration with different molecular weight cutoffs, suggesting small molecules from Listeria might be the chemical cues to attract protozoa. Headspace volatile organic compounds (VOC) released from Listeria were collected, spiked to 0.1% peptone and tested as the chemotactic effectors. It was discovered that the Euglena cells responded quickly to Listeria VOCs including decanal, 3,5- dimethylbenzaldehyde, ethyl acetate, indicating bacterial VOCs were used by Euglena to track the location of bacteria. [ABSTRACT FROM AUTHOR]

South Korea is ranked as 4th among 34 nations of the Organization for Economic Cooperation and Development with 102 deaths in road accidents per one million population. This paper aims to investigate the factors associated with road accidents in South Korea. The rainfall data of the Korea Meteorological Administration and road accidents data of Traffic Accident Analysis System of Korea Road Traffic Authority is analyzed for this purpose. In this connection, multivariate regression analysis and ratio analysis with the descriptive analysis are performed to uncover the catastrophic factors involved. In turn, the results reveal that traffic volume is the leading factor in road accidents. The limited road extension of 1.47% compared to the 4.14% per annum growth of the vehicles is resulting in road accidents at such a large scale. The increasing proportion of passenger cars accelerate road accidents as well. 56% of accidents occur by the infringement of safety driving violations. The drivers with higher driving experience tend to have a higher accident ratio. The collected data is analyzed in terms of gender, driver experience, type of violations and accidents as well as the associated time of the accidents when they happen. The results indicate that 36.29% and 53.01% of accidents happen by male drivers in the day and night time, respectively. 29.15% of crashes happen due to safety infringement and violations of 41 to 60 years old drivers. The results demonstrate that population density is associated with the accidents frequency and lower density results in an increased number of accidents. The necessity of the state-of-the-art regulations to govern the urban road traffic is beyond dispute, and it becomes even more crucial for citizens’ relief since in our daily lives road accidents are getting more diverse. [ABSTRACT FROM AUTHOR]

Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of hapten-specific memory T cells has been well-established, recent research in mice has expanded the “adaptive” characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system. [ABSTRACT FROM AUTHOR]

Phytophthora capsici is a soil borne pathogen, and is among the most destructive pathogens for Capsicum annuum (chile). P. capsici is known to cause diseases on all parts of the chile plants. Therefore, it requires independent resistance genes to control disease symptoms that are induced by each of the P. capsici strains. This requirement of multiple resistance genes to confer resistance to P. capsici, in chile makes breeding for resistance a daunting pursuit. Against this backdrop, a genetic engineering approach would be to introduce a broad host resistance gene into chile in order to protect it from different races of P. capsici. Notably, a broad host resistance gene RB from Solanum bulbocastanum has been shown to confer resistance to P. infestans in both S. tuberosum and S. lycopersicum. We agroinfiltrated the RB gene into the leaves of susceptible chile plants, demonstrating that the gene is also capable of lending resistance to P. capsici in chile. We introduced the RB gene into chile by developing an Agrobacterium tumefaciens mediated transformation system. The integration of the RB gene into the genome of the primary transformants and its subsequent transfer to the F1 generation was confirmed by genomic PCR using primers specific for the RB gene. A 3:1 ratio for the presence and absence of the RB gene was observed in the F1 progeny. In addition to showing resistance to P. capsici in a leaf inoculation experiment, about 30% of the F1 progeny also exhibited resistance to root inoculation. Our data, when taken together, suggests that the RB gene from S. bulbocastanum confers resistance against P. capsici in C. annuum, thereby demonstrating that the RB gene has an even broader host range than reported in the literature–both in terms of the host and the pathogen. [ABSTRACT FROM AUTHOR]

Purpose: Decreasing the risk of catheter related bloodstream infections (CRBSIs) remains a key focus for improving outcomes and reducing cost of care for hemodialysis (HD) patients. Recent studies demonstrate CRBSI rates can be improved by managing bacterial colonization at the catheter exit site. Herein we present the results of a study documenting the clinical performance of the NexSite HD catheter, a new tunneled central venous catheter which incorporates Exit Site Management (ESM) technology. Methods: We conducted an observational study using a prospective, multi-center registry of HD patients implanted with the NexSite HD catheter. The primary endpoint for the study was CRBSI rate for a period up to 180-days following catheter placement. Secondary endpoints included device placement success rate, exit site healing, development of an exit site or tunnel infection, and early or late non-infectious catheter-related complications. All reasons for early non-elective catheter removal were recorded. Results: A total of 115 HD patients at 6 sites were included in the final analysis. Cumulative catheter use was 10,924 days with a mean duration of 95 days. Seven patients experienced CRBSIs during the study period resulting in a CRBSI rate of 0.64 per 1,000 catheter-days. Seventy-four patients (64.3%) had either elective catheter removal (n = 56) or utilized the catheter for the entire 180-day observation period (n = 18). Thirty-five patients (30%) underwent non-elective device removal either due to CRBSI (n = 5), low flow (n = 16), exit site issues (n = 7), or for other causes (n = 7). Six patients died during the observation period with 1 death due to CRBSI-associated complications and the remaining 5 deaths attributed to non-device related causes. Conclusion: Our findings demonstrate that the NexSite HD catheter equipped with ESM technology can achieve a CRBSI rate in compliance with the NKF KDOQI (National Kidney Foundation Kidney Disease Outcome Quality Initiatives) Clinical Performance Guidelines stated goal of less than 1.0/1,000 catheter-days when used in hemodialysis patients using current standard of care nursing protocols. [ABSTRACT FROM AUTHOR]

Vehicles can be classified by configuration as either bonnet-type or cab-over type according to engine location. Compared to bonnet-type, the front compartment of cab-over type vehicles is considerably shorter; thus, it may be less likely to absorb the energy generated in a collision, and in turn be unable to prevent deformation of the occupant space and protect occupants from injury. This study was a cohort study involving 943 occupants of mini-vehicles who were injured in frontal collision accidents between 2001 and 2015 and transferred to Ohta Nishinouchi Hospital. The vehicle configuration was divided into bonnet-type and cab-over type (i.e., truck-type and wagon-type). The tested outcomes were anatomical-specific severe injury of the pelvis and extremities, the head and neck, the abdomen, and the chest. To estimate adjusted odds ratios (AOR) for associations between vehicle configuration and anatomical-specific severe injury, we fitted generalized estimating equations for each outcome. Compared with bonnet-type vehicles, a greater risk of serious pelvis and extremities injury was found for both truck (AOR: 2.21; 95% Confidence Interval [95% CI]: 1.22–4.00) and wagon-type vehicles (AOR: 3.43; 95%CI 1.60–7.39). For serious head and neck injury, truck-type vehicles were associated with greater risk (AOR: 2.04; 95% CI: 1.10–3.79) than bonnet-type vehicles, whereas wagon-type vehicles were not. Compared with the occupants of bonnet-type vehicles, cab-over type vehicle occupants were more likely to have serious pelvis and extremities injury during frontal collisions. Additionally, truck-type vehicle occupants were more likely to have serious head and neck injury than bonnet-type vehicle occupants. These findings are expected to promote safer behaviors for vehicle occupants and the automobile industry. [ABSTRACT FROM AUTHOR]

Asparagus stem wilt, is a significant and devastating disease, typically leading to extensive economic losses in the asparagus industry. To obtain transgenic plants resistant to stem wilt, the hevein-like gene, providing broad spectrum bacterial resistance was inserted into the asparagus genome through Agrobacterium tumefaciens-mediated transformation. The optimal genetic transformation system for asparagus was as follows: pre-culture of embryos for 2 days, inoculation using a bacterial titre of OD600 = 0.6, infection time 10 min and co-culturing for 4 days using an Acetosyringone concentration of 200 μmol/L. Highest transformation frequencies reached 21% and ten transgenic asparagus seedlings carrying the hevein-like gene were identified by polymerase chain reaction. Moreover, integration of the hevein-like gene in the T1 generation of transgenic plants was confirmed by southern blot hybridization. Analysis showed that resistance to stem wilt was enhanced significantly in the transgenic plants, in comparison to non- transgenic plants. The results provide additional data for genetic improvement and are of importance for the development of new disease-resistant asparagus varieties. [ABSTRACT FROM AUTHOR]

While road safety in the United States (U.S.) has been continually improving since the 1970's, there are indications that these improvements are becoming increasingly difficult to sustain. Strategic Highway Safety Plans (SHSPs) are prepared by States to guide road safety management, however assessing the appropriateness of these plans remains a significant challenge, especially for the future in which they are to be applied. This study developed a new methodology to assess SHSPs from the perspectives of comprehensive system-based safety management and relevant future issues that can be applied before SHSPs are implemented, thereby avoiding long periods after implementation before assessing the appropriateness of the plans. A rating scale was developed and applied to assess 48 U.S. SHSPs against two key criteria: 1. a comprehensive framework for road safety, and 2. the anticipated changing, difficult and unpredictable nature of future transport and its context. The analysis concluded that current SHSPs have good national oversight with several strengths but were weak in some areas of content and did not address future challenges. Improvements are suggested to strengthen the plans’ thoroughness by being consistent with systems theory and practice, as well as ways that these SHSPs can be more resilient to future circumstances. Implementing the recommendations in this paper provides the opportunity to adopt a system-based safety management practice that has been successful in other hazardous industries. Doing so is expected to most efficiently and effectively continue the recent improvements to road safety, which is likely to be increasingly difficult otherwise. [ABSTRACT FROM AUTHOR]

Chronic wasting disease (CWD) is a fatal prion disease that can infect deer, elk and moose. CWD has now been detected in 26 states of the USA, 3 Canadian provinces, South Korea, Norway, Sweden and Finland. CWD continues to spread from endemic areas, and new foci of infections are frequently detected. As increasing numbers of cervids become infected, the likelihood for human exposure increases. To date, no cases of CWD infection in humans have been confirmed, but experience with the BSE zoonosis in the United Kingdom suggests exposure to CWD should be minimized. Specifically, hunters, meat processors and others in contact with tissues from potentially CWD-infected cervids need a practical method to decontaminate knives, saws and other equipment. Prions are notoriously difficult to inactivate, and most effective methods require chemicals or sterilization processes that are either dangerous, caustic, expensive or not readily available. Although corrosive, sodium hypochlorite (bleach) is widely available and affordable and has been shown to inactivate prion agents including those that cause scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. In the current study, we confirm that bleach is an effective disinfectant for CWD prions and establish minimum times and bleach concentrations to eliminate prion seeding activity from stainless steel and infected brain homogenate solutions. We found that a five-minute treatment with a 40% dilution of household bleach was effective at inactivating CWD seeding activity from stainless-steel wires and CWD-infected brain homogenates. However, bleach was not able to inactivate CWD seeding activity from solid tissues in our studies. [ABSTRACT FROM AUTHOR]

Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc) is a systemic bacterial disease that affects citrus plantations globally. Biotic stress in plants has been linked to a group of important transcription factors known as Basic Leucine Zippers (BZIPs). In this study, CsBZIP40 was functionally characterized by expression analysis, including induction by Xcc and hormones, subcellular localization, over-expression and RNAi silencing. CsBZIP40 belongs to group D of the CsBZIP family of transcription factors and localizes in the nucleus, potentially serving as a transcriptional regulator. In wild type (WT) plants CsBZIP40 can be induced by plant hormones in addition to infection by Xcc which has given insight into its involvement in CBC. In the present study, over-expression of CsBZIP40 conferred resistance to Xcc while its silencing led to Xcc susceptibility. Both over-expression and RNAi affected salicylic acid (SA) production and expression of the genes involved in the SA synthesis and signaling pathway, in addition to interaction of CsBZIP40 with CsNPR1, as detected by a GST pull-down assay. Taken together, the results of this study confirmed the important role of CsBZIP40 in improving resistance to citrus canker through the SA signaling pathway by the presence of NPR1 to activate PR genes. Our findings are of potential value in the breeding of tolerance to CBC in citrus fruits. [ABSTRACT FROM AUTHOR]

Echolocation is the detection and localization of objects by listening to the sounds they reflect. Early studies of human echolocation used real objects that the experimental leader positioned manually before each experimental trial. The advantage of this procedure is the use of realistic stimuli; the disadvantage is that manually shifting stimuli between trials is very time consuming making it difficult to use psychophysical methods based on the presentation of hundreds of stimuli. The present study tested a new automated system for stimulus presentation, the Echobot, that overcomes this disadvantage. We tested 15 sighted participants with no prior experience of echolocation on their ability to detect the reflection of a loudspeaker-generated click from a 50 cm circular aluminum disk. The results showed that most participants were able to detect the sound reflections. Performance varied considerably, however, with mean individual thresholds of detection ranging from 1 to 3.2 m distance from the disk. Three participants in the loudspeaker experiment also tested using self-generated vocalization. One participant performed better using vocalization and one much worse than in the loudspeaker experiment, illustrating that performance in echolocation experiments using vocalizations not only measures the ability to detect sound reflections, but also the ability to produce efficient echolocation signals. Overall, the present experiments show that the Echobot may be a useful tool in research on human echolocation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of topical mydriatic eye drops on optical coherence tomography angiography (OCTA) parameters in patients with age-related macular degeneration (AMD). Methods: 27 eyes of 27 patients suffering from AMD were included in this cross-sectional study. Patients with ≥-4.5 diopters spherical equivalent, corneal opacities or dense cataract preventing high-quality imaging were excluded. Whole-en-face scans of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the central 3x3mm foveal region as well as whole-en-face and peripapillary scans of the radial peripapillary capillaries (RPC) were generated using OCTA (AngioVue®, Optovue). Imaging was first conducted with patients’ eyes in miosis, then in mydriasis after instillation of a dilating eye drop (0.5% tropicamide, 2.5% phenylephrine-HCl). Main outcome measures were flow density (FD), foveal avascular zone (FAZ), signal strength index (SSI) and motion artifact score (MAS). Results: Our results reveal that in AMD patients there is no significant difference between FD measurements taken in miosis and those taken in mydriasis around the SCP (p = 0.198), DCP (p = 0.458), RPC whole-en-face (p = 0.275) and RPC peripapillary (p = 0.503). Measurements taken in these two states appear to be equivalent for assessment of FD (90%CI within ± 0.05). No significant difference was found either in the area of the FAZ (p = 0.338) or in the SSI (p = 0.371) before and after the instillation of tropicamide/phenylephrine. MAS was significantly lower after the application of mydriatic eye drops (p = 0.003). Conclusions: Our findings reveal that neither measurements of FD nor measurements of the FAZ area changed significantly in AMD patients after the application of tropicamide/phenylephrine. Since MAS improved significantly in dilation, mydriatic examination is recommended. Nevertheless, a comparison of OCTA metrics from images taken with different pupil states (miosis versus mydriasis) is valid for clinical trials. [ABSTRACT FROM AUTHOR]

Motor cortical beta activity (13–30 Hz) is a hallmark signature of healthy and pathological movement, but its behavioural relevance remains unclear. Using high-precision magnetoencephalography (MEG), we show that during the classical event-related desynchronisation (ERD) and event-related synchronisation (ERS) periods, motor cortical beta activity in individual trials (n > 12,000) is dominated by high amplitude, transient, and infrequent bursts. Beta burst probability closely matched the trial-averaged beta amplitude in both the pre- and post-movement periods, but individual bursts were spatially more focal than the classical ERS peak. Furthermore, prior to movement (ERD period), beta burst timing was related to the degree of motor preparation, with later bursts resulting in delayed response times. Following movement (ERS period), the first beta burst was delayed by approximately 100 milliseconds when an incorrect response was made. Overall, beta burst timing was a stronger predictor of single trial behaviour than beta burst rate or single trial beta amplitude. This transient nature of motor cortical beta provides new constraints for theories of its role in information processing within and across cortical circuits, and its functional relevance for behaviour in both healthy and pathological movement. [ABSTRACT FROM AUTHOR]

Quantitative genomic and proteomic evaluation of human latent fingerprint depositions represents a challenge within the forensic field, due to the high variability in the amount of DNA and protein initially deposited. To better assess recovery techniques for touch depositions, we present a method to produce simple and customizable artificial fingerprints. These artificial fingerprint samples include the primary components of a typical latent fingerprint, specifically sebaceous fluid, eccrine perspiration, extracellular DNA, and proteinaceous epidermal skin material (i.e., shed skin cells). A commercially available emulsion of sebaceous and eccrine perspiration material provides a chemically-relevant suspension solution for fingerprint deposition, simplifying artificial fingerprint production. Extracted human genomic DNA is added to accurately mimic the extracellular DNA content of a typical latent print and comparable DNA yields are recovered from the artificial prints relative to human prints across surface types. Capitalizing on recent advancements in the use of protein sequence identification for human forensic analysis, these samples also contain a representative quantity of protein, originating from epidermal skin cells collected from the fingers and palms of volunteers. Proteomic sequencing by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis indicates a high level of protein overlap between artificial and latent prints. Data are available via ProteomeXchange with identifier PXD015445. By including known quantities of DNA and protein into each artificial print, this method enables total DNA and protein recovery to be quantitatively assessed across different sample collection and extraction methods to better evaluate extraction efficiency. Collectively, these artificial fingerprint samples are simple to make, highly versatile and customizable, and accurately represent the biochemical composition and biological signatures of human fingerprints. [ABSTRACT FROM AUTHOR]

Background: Discontinuous electroencephalographic activity in children is thought to reflect brain inactivation. Discontinuity has been observed in states of pathology, where it is predictive of adverse neurological outcome, as well as under general anesthesia. Though in preterm-infants discontinuity reflects normal brain development, less is known regarding its role in term children, particularly in the setting of general anesthesia. Here, we conduct a post-hoc exploratory analysis to investigate the spectral features of discontinuous activity in children under general anesthesia. Methods: We previously recorded electroencephalography in children less than forty months of age under general anesthesia (n = 65). We characterized the relationship between age, anesthetic depth, and discontinuous activity, and used multitaper spectral methods to compare the power spectra of subjects with (n = 35) and without (n = 30) discontinuous activity. In the subjects with discontinuous activity, we examined the amplitude and power spectra associated with the discontinuities and analyzed how these variables varied with age. Results: Cumulative time of discontinuity was associated with increased anesthetic depth and younger age. In particular, age-matched children with discontinuity received higher doses of propofol during induction as compared with children without discontinuity. In the tens of seconds preceding the onset of discontinuous activity, there was a decrease in high-frequency power in children four months and older that could be visually observed with spectrograms. During discontinuous activity, there were distinctive patterns of amplitude, spectral edge, and power in canonical frequency bands that varied with age. Notably, there was a decline in spectral edge in the seconds immediately following each discontinuity. Conclusion: Discontinuous activity in children reflects a state of a younger or more deeply anesthetized brain, and characteristic features of discontinuous activity evolve with age and may reflect neurodevelopment. [ABSTRACT FROM AUTHOR]

Visual hand gesture recognition systems are promising technologies for Human Computer Interaction, as they allow a more immersive and intuitive interaction. Most of these systems are based on the analysis of skeleton information, which is in turn inferred from color, depth, or near-infrared imagery. However, the robust extraction of skeleton information from images is only possible for a subset of hand poses, which restricts the range of gestures that can be recognized. In this paper, a real-time hand gesture recognition system based on a near-infrared device is presented, which directly analyzes the infrared imagery to infer static and dynamic gestures, without using skeleton information. Thus, a much wider range of hand gestures can be recognized in comparison with skeleton-based approaches. To validate the proposed system, a new dataset of near-infrared imagery has been created, from which good results that outperform other state-of-the-art strategies have been obtained. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are one of the most common infections in older people and are associated with increased morbidity and mortality. UTIs are also associated with increased risk of antimicrobial resistance (AR). This study examined changes in AR among older inpatients with a primary diagnosis of UTIs in the United States over an 8-year period and the impact of AR on clinical outcomes and hospital costs. Data were obtained from the longitudinal hospital HCUP-NIS database from 2009 to 2016 for inpatient episodes that involved those aged 65+ years. The ICD-9 and ICD-10 codes were used to identify episodes with a primary diagnosis of UTIs, comorbidities, AR status and age-adjusted Deyo-Charlson comorbidity index (ACCI) for the patient concerned. Weighted multivariable regression was used to examine the impact of AR on all-cause inpatient mortality, discharge destination, length of stay and hospital expenditures, adjusted for socio-demographic and clinical covariates. The proportion of admissions with AR increased, from 3.64% in 2009 to 6.88% in 2016 (p<0.001), with distinct patterns for different types of resistance. The likelihood of AR was higher in admissions with high ACCI scores and admissions to hospitals in urban areas. Admissions with AR were more likely to be discharged to healthcare facilities (e.g. care homes) compared to routine discharge (OR 1.81; 95%CI, 1.75–1.86), had increased length of stay (1.12 days; 95%CI, 1.06–1.18) and hospital costs (1259 USD; 95%CI, 1178–1340). Resistance due to MRSA was specifically associated with increased hospital mortality (OR 1.33; 95%CI, 1.15–1.53). Our findings suggest that the prevalence of AR has increased among older inpatients with UTIs in the USA. The study highlights the impact of AR among older inpatients with a primary diagnosis of UTIs on clinical outcomes and hospital costs. These relationships and their implications for the care homes to which patients are frequently discharged warrant further research. [ABSTRACT FROM AUTHOR]

We developed an automated 2-tiered Fuhrman’s grading system for clear cell renal cell carcinoma (ccRCC). Whole slide images (WSI) and clinical data were retrieved for 395 The Cancer Genome Atlas (TCGA) ccRCC cases. Pathologist 1 reviewed and selected regions of interests (ROIs). Nuclear segmentation was performed. Quantitative morphological, intensity, and texture features (n = 72) were extracted. Features associated with grade were identified by constructing a Lasso model using data from cases with concordant 2-tiered Fuhrman’s grades between TCGA and Pathologist 1 (training set n = 235; held-out test set n = 42). Discordant cases (n = 118) were additionally reviewed by Pathologist 2. Cox proportional hazard model evaluated the prognostic efficacy of the predicted grades in an extended test set which was created by combining the test set and discordant cases (n = 160). The Lasso model consisted of 26 features and predicted grade with 84.6% sensitivity and 81.3% specificity in the test set. In the extended test set, predicted grade was significantly associated with overall survival after adjusting for age and gender (Hazard Ratio 2.05; 95% CI 1.21–3.47); manual grades were not prognostic. Future work can adapt our computational system to predict WHO/ISUP grades, and validating this system on other ccRCC cohorts. [ABSTRACT FROM AUTHOR]

Background and objective: To take full advantage of decision support, machine learning, and patient-level prediction models, it is important that models are not only created, but also deployed in a clinical setting. The KETOS platform demonstrated in this work implements a tool for researchers allowing them to perform statistical analyses and deploy resulting models in a secure environment. Methods: The proposed system uses Docker virtualization to provide researchers with reproducible data analysis and development environments, accessible via Jupyter Notebook, to perform statistical analysis and develop, train and deploy models based on standardized input data. The platform is built in a modular fashion and interfaces with web services using the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard to access patient data. In our prototypical implementation we use an OMOP common data model (OMOP-CDM) database. The architecture supports the entire research lifecycle from creating a data analysis environment, retrieving data, and training to final deployment in a hospital setting. Results: We evaluated the platform by establishing and deploying an analysis and end user application for hemoglobin reference intervals within the University Hospital Erlangen. To demonstrate the potential of the system to deploy arbitrary models, we loaded a colorectal cancer dataset into an OMOP database and built machine learning models to predict patient outcomes and made them available via a web service. We demonstrated both the integration with FHIR as well as an example end user application. Finally, we integrated the platform with the open source DataSHIELD architecture to allow for distributed privacy preserving data analysis and training across networks of hospitals. Conclusion: The KETOS platform takes a novel approach to data analysis, training and deploying decision support models in a hospital or healthcare setting. It does so in a secure and privacy-preserving manner, combining the flexibility of Docker virtualization with the advantages of standardized vocabularies, a widely applied database schema (OMOP-CDM), and a standardized way to exchange medical data (FHIR). [ABSTRACT FROM AUTHOR]

The general population is exposed to bisphenol A (BPA) orally, parenterally, transdermally, and environmentally as a result of the use of BPA in food packaging, plastics, and personal care products. The majority of the population nowadays (91–99%) has detectable levels of BPA inside their body. In this study, we successfully performed an inexpensive, rapid, and simple protein precipitation procedure for extraction of BPA from human plasma, followed by analysis by LC-MS/MS. This method was specifically developed for handling large numbers of samples with minimum cost and volume of sample. The developed method was accurate, precise, and reproducible for quantification of BPA from human plasma samples in the concentration range of 10–2000 ng/mL. The method was performed on samples from 150 healthy volunteers who were enrolled in the study. The mean of observed BPA level was 2.22 ± 9.91 ng/mL. Higher BPA levels were observed for females compare to that of males (p-value = 0.002), the BPA levels were higher in participants 33 years of age and older compared to those less than 33 years of age (p-value = 0.000), then the BPA levels higher in subjects with tap water as source of drinking (p-value = 0.005). This method may be valuable for general risk assessment of BPA for a large and varied population because of its efficiency and economical aspects. [ABSTRACT FROM AUTHOR]

Rationale: Multiple clinical trials support the effectiveness of cardiac resynchronization therapy (CRT); however, optimal patient selection remains challenging due to substantial treatment heterogeneity among patients who meet the clinical practice guidelines. Objective: To apply machine learning to create an algorithm that predicts CRT outcome using electronic health record (EHR) data avaible before the procedure. Methods and results: We applied machine learning and natural language processing to the EHR of 990 patients who received CRT at two academic hospitals between 2004–2015. The primary outcome was reduced CRT benefit, defined as <0% improvement in left ventricular ejection fraction (LVEF) 6–18 months post-procedure or death by 18 months. Data regarding demographics, laboratory values, medications, clinical characteristics, and past health services utilization were extracted from the EHR available before the CRT procedure. Bigrams (i.e., two-word sequences) were also extracted from the clinical notes using natural language processing. Patients accrued on average 75 clinical notes (SD, 29) before the procedure including data not captured anywhere else in the EHR. A machine learning model was built using 80% of the patient sample (training and validation dataset), and tested on a held-out 20% patient sample (test dataset). Among 990 patients receiving CRT the mean age was 71.6 (SD, 11.8), 78.1% were male, 87.2% non-Hispanic white, and the mean baseline LVEF was 24.8% (SD, 7.69). Out of 990 patients, 403 (40.7%) were identified as having a reduced benefit from the CRT device (<0% LVEF improvement in 25.2%, death by 18 months in 15.6%). The final model identified 26% of these patients at a positive predictive value of 79% (model performance: Fβ (β = 0.1): 77%; recall 0.26; precision 0.79; accuracy 0.65). Conclusions: A machine learning model that leveraged readily available EHR data and clinical notes identified a subset of CRT patients who may not benefit from CRT before the procedure. [ABSTRACT FROM AUTHOR]

Alternative splicing diversifies mRNA transcripts in human cells. While the spliceosome pairs exons with a high degree of accuracy, the rates of rare aberrant and non-canonical pre-mRNA splicing have not been evaluated at the nucleotide level to determine the quantity and identity of these events across splice junctions. Using ultra-deep sequencing the frequency of aberrant and non-canonical splicing events for three splice junctions flanking exon 7 of SMN1 were determined at single nucleotide resolution. After correction for background noise introduced by PCR amplification and sequencing steps, pre-mRNA splicing was shown to maintain a low overall rate of aberrant and non-canonically spliced events. Several previously unannotated splicing events across 3 exon|intron junctions in SMN1 were identified. Mutations within SMN exon 7 were shown to affect splicing fidelity by modulating RNA secondary structures, by altering the binding site of regulatory proteins and by changing the 5’ splice site strength. Mutations also create a truncated SMN1 exon 7 through the introduction of a de novo non-canonical 5’ splice site. The results from the ultra-deep sequencing approach highlight the impressive fidelity of pre-mRNA splicing and demonstrate that the immediate sequence context around splice sites is the main driving force behind non-canonical splice site pairing. [ABSTRACT FROM AUTHOR]

Humans can recall various aspects of a characteristic sound as a whole when they see a visual shape stimulus that has been intimately associated with the sound. In subjects with audio-visual associative memory, auditory responses that code the associated sound may be induced in the auditory cortex in response to presentation of the associated visual shape stimulus. To test this possibility, mice were pre-exposed to a combination of an artificial sound mimicking a cat’s “meow” and a visual shape stimulus of concentric circles or stars for more than two weeks, since such passive exposure is known to be sufficient for inducing audio-visual associative memory in mice. After the exposure, we anesthetized the mice, and presented them with the associated visual shape stimulus. We found that associative responses in the auditory cortex were induced in response to the visual stimulus. The associative auditory responses were observed when complex sounds such as “meow” were used for formation of audio-visual associative memory, but not when a pure tone was used. These results suggest that associative auditory responses in the auditory cortex represent the characteristics of the complex sound stimulus as a whole. [ABSTRACT FROM AUTHOR]

Background: The number of periprosthetic joint infections (PJI) after total knee arthroplasty (TKA) is increasing annually. Animal models have been used to clarify their clinical characteristics and the infection mechanism of pathogenic bacteria, However, since the prosthesis design of animal models is not uniform, it is difficult to simulate the environment of clinical PJI. Objectives: To retrospect the progress on the prosthesis design of animal models of PJI after TKA and to summarize the criteria for evaluating a clinically representative model of PJI. Methods: This systematic review was reported on the basis of Systematic Reviews and Meta-Analyzes (PRISMA). Pubmed, EMbase, Cochrane Library, Web of Science, Wanfang Data and China National Knowledge Infrastructure were researched for animal models of PJI after TKA from database establishment to April 2019 according to Chinese and English retrieval words, including “periprosthetic joint infections and total knee arthroplasty,” “periprosthetic joint infections and model,” “periprosthetic joint infections and biofilm,” and “total knee arthroplasty and model.” Results: A total of 12 quantitative studies were enrolled in our study finally: 8 representative studies described prosthesis designs used in PJI animal models, 4 studies described prosthesis designs in non-infected animal models which were suitable for infection models. The major problems need to be dealed with were prosthesis, installation location, material, the function of separating the articular and medullary cavity, fixation manner, and the procedure of preserving the posterior cruciate ligament. Conclusion: A highly representative design of the animal prosthesis of PJI should meet the following criteria: the surface of the prosthesis is smooth with the formation of biofilm, composed of titanium-6Al-4V or cobalt-chromium-molybdenum alloy; prosthesis can bear weight and is highly stable; and it can connect the joint cavity and medullary cavity simultaneously. To reach a more reliable conclusion, further experiments and improvements are required. [ABSTRACT FROM AUTHOR]

There is a vivid research on securely deliver a secret message by using a data hiding technique in digital images. However, most existing solutions of data-hiding need to encrypt secret data first, and embed the encrypt message into cover image, which is not promising any security once the embedding algorithm is leaked. In this paper, an efficient and adaptive data hiding scheme is presented which is based on a new reference matrix named secure reference matrix. The scheme is flexible enough to meet different data hiding capacities and image quality as needed, and we allow the reference matrix to be more secure since it is randomly generated each time and make it much harder for being attack with exhaustive manner by extending the possible solution. We give the detail protocol for our scheme and provide the practical test and performance analysis. Experimental results show that our scheme has a better flexibility and efficiency in embedding process, and the average value of Peak Signal to Noise Ratio (PSNR) for the stego-images which are generated by our scheme have a higher visual quality for different embedding capacities, and our scheme is more efficient compared with related work. [ABSTRACT FROM AUTHOR]

Non-invasive fetal electrocardiography (NI-FECG) plays an important role in fetal heart rate (FHR) measurement during the pregnancy. However, despite the large number of methods that have been proposed for adult ECG signal processing, the analysis of NI-FECG remains challenging and largely unexplored. In this study, we propose a prefix tree-based framework, called QRStree, for FHR measurement directly from the abdominal ECG (AECG). The procedure is composed of three stages: Firstly, a preprocessing stage is employed for noise elimination. Secondly, the proposed prefix tree-based method is used for fetal QRS complexes (FQRS) detection. Finally, a correction stage is applied for false positive and false negative correction. The novelty of the framework relies on using the range of FHR to establish the connections between the FQRS. The consecutive FQRS can be considered as strings composed of alphabet items, thus we can use the prefix tree to store them. A vertex of the tree contains an alphabet, thus a path of the tree gives a string. Such that, by storing the connections of the FQRS into the prefix tree structure, the problem of FQRS detection converts to a problem of optimal path selection. Specifically, after selecting the optimal path of the tree, the nodes in the optimal path are collected as detected FQRS. Since the prefix tree can cover every possible combination of the FQRS candidates, it has the potential to reduce the occurrence of miss detections. Results on two different databases show that the proposed method is effective in FHR measurement from single-channel AECG. The focus on single-channel FHR measurement facilitates the long-term monitoring for healthcare at home. [ABSTRACT FROM AUTHOR]

The R package crossrun computes the joint distribution of the number of crossings and the longest run in a sequence of independent Bernoulli observations. The main intended application is statistical process control where the joint distribution may be used for systematic investigation, and possibly refinement, of existing rules for distinguishing between signal and noise. While the crossrun vignette is written to assist in practical use, this article gives a hands-on explanation of why the procedures works. The article also includes a discussion of limitations of the present version of crossrun together with an outline of ongoing work to meet these limitations. There is more to come, and it is necessary to grasp the basic ideas behind the procedure implemented both to understand these planned extensions, and how presently implemented rules in statistical process control, based on the number of crossings and the longest run, may be refined. [ABSTRACT FROM AUTHOR]

Human neonates spontaneously associate changes in magnitude across the dimensions of number, length, and duration. Do these particular associations generalize to other pairs of magnitudes in the same way at birth, or do they reflect an early predisposition to expect specific relations between spatial, temporal, and numerical representations? To begin to answer this question, we investigated how strongly newborns associated auditory sequences changing in number/duration with visual objects changing in levels of brightness. We tested forty-eight newborn infants in one of three, bimodal stimulus conditions in which auditory numbers/durations increased or decreased from a familiarization trial to the two test trials. Auditory numbers/durations were paired with visual objects in familiarization that remained the same on one test trial but changed in luminance/contrast or shape on the other. On average, results indicated that newborns looked longer when changes in brightness accompanied the number/duration change as compared to no change, a preference that was most consistent when the brightness change was congruent with the number/duration change. For incongruent changes, this preference depended on trial order. Critically, infants showed no preference for a shape change over no shape change, indicating that infants likely treated brightness differently than a generic feature. Though this performance pattern is somewhat similar to previously documented associations, these findings suggest that cross-magnitude associations among number, length, and duration may be more specialized at birth, rather than emerge gradually from postnatal experience or maturation. [ABSTRACT FROM AUTHOR]