Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimizing antimicrobial therapy in critically ill patients

Critically ill patients with infection in the intensive care unit (ICU) would certainly benefit from timely bacterial identification and effective antimicrobial treatment. Diagnostic techniques have clearly improved in the last years and allow earlier identification of bacterial strains in some cases, but these techniques are still quite expensive and not readily available in all institutions. Moreover, the ever increasing rates of resistance to antimicrobials, especially in Gram-negative pathogens, are threatening the outcome for such patients because of the lack of effective medical treatment; ICU physicians are therefore resorting to combination therapies to overcome resistance, with the direct consequence of promoting further resistance. A more appropriate use of available antimicrobials in the ICU should be pursued, and adjustments in doses and dosing through pharmacokinetics and pharmacodynamics have recently shown promising results in improving outcomes and reducing antimicrobial resistance. The aim of multidisciplinary antimicrobial stewardship programs is to improve antimicrobial prescription, and in this review we analyze the available experiences of such programs carried out in ICUs, with emphasis on results, challenges, and pitfalls. Any effective intervention aimed at improving antibiotic usage in ICUs must be brought about at the present time; otherwise, we will face the challenge of intractable infections in critically ill patients in the near future.
The Clinical Characteristics and Predictors of Refractory Mycoplasma pneumoniae Pneumonia in Children

Objective To analyze the clinical characteristics of refracory Mycoplasma pneumoniae pneumonia (RMPP), and explore the related factors predicting RMPP. Methods Retrospective analysis was performed on 634 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in our hospital between January 1, 2011 and December 31, 2014. The clinical features, laboratory data, radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and the predictive values of related factors were analyzed. Results The median age of the RMPP patients (n = 145) was much older than that of the GMPP patients (n = 489) (P<0.01). We also found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in RMPP group, which needed oxygen more often, longer antibiotics administration and intensive care (P<0.05). Meanwhile, the levels of C-reactive protein (CRP), lactic dehydrogenase (LDH), immunoglobulin A (IgM), interleukin (IL)-6, IL-10, interferon gamma (IFN-γ) and the percentage of neutrophils, CD8+ in RMPP group were significantly higher than those in GMPP group (P<0.05); while the levels of prealbumin (PAB) were lower than that in GMPP group (P<0.01). In ROC curve analysis, the percentage of neutrophil, CRP, LDH, PAB, IL-6, IL-10 and IFN-γ were useful for differentiating patients with RMPP from those with GMPP. Multiple logistic regression analysis showed that the CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml were significant predictors regarding to RMPP. Conclusions CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml might be the significant predictors of RMPP in children, which can aid in early recognition of RMPP.
Cryopreservation in mammalian conservation biology: current applications and potential utility

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress. com/permissions.php Research and Reports in Biodiversity Studies 2015:4 1–8 Research and Reports in Biodiversity Studies Dovepress
Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus

ABSTRACT The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmission by using statistical analyses of variants identified in pathogen sequencing data. These analyses, however, did not account for variant calling thresholds and stochastic viral replication dynamics within recipient hosts. Because these factors can skew bottleneck size estimates, we introduce a new method for inferring bottleneck sizes that accounts for these factors. Through the use of a simulated data set, we first show that our method, based on beta-binomial sampling, accurately recovers transmission bottleneck sizes, whereas other methods fail to do so. We then apply our method to a data set of influenza A virus (IAV) infections for which viral deep-sequencing data from transmission pairs are available. We find that the IAV transmission bottleneck size estimates in this study are highly variable across transmission pairs, while the mean bottleneck size of 196 virions is consistent with a previous estimate for this data set. Furthermore, regression analysis shows a positive association between estimated bottleneck size and donor infection severity, as measured by temperature. These results support findings from experimental transmission studies showing that bottleneck sizes across transmission events can be variable and influenced in part by epidemiological factors. IMPORTANCE The transmission bottleneck size describes the size of the pathogen population transferred from the donor to the recipient host and may affect the rate of pathogen adaptation within host populations. Recent advances in sequencing technology have enabled bottleneck size estimation from pathogen genetic data, although there is not yet a consistency in the statistical methods used. Here, we introduce a new approach to infer the bottleneck size that accounts for variant identification protocols and noise during pathogen replication. We show that failing to account for these factors leads to an underestimation of bottleneck sizes. We apply this method to an existing data set of human influenza virus infections, showing that transmission is governed by a loose, but highly variable, transmission bottleneck whose size is positively associated with the severity of infection of the donor. Beyond advancing our understanding of influenza virus transmission, we hope that this work will provide a standardized statistical approach for bottleneck size estimation for viral pathogens.
Arbitrage-free Models In Markets With Transaction Costs

In the paper [7], Guasoni studies financial markets which are subject to proportional transaction costs. The standard martingale framework of stochastic finance is not applicable in these markets, since the transaction costs force trading strategies to have bounded variation, while continuous- time martingale strategies have infinite transaction cost. The main question that arises out of [7] is whether it is possible to give a convenient condition to guarantee that a trading strategy has no arbitrage. Such a condition was proposed and studied in [6] and [1], the so-called stickiness property, whereby an asset's price is never certain to exit a ball within a predetermined finite time. In this paper, we define the multidimensional extension of the stickiness property, to handle arbitrage-free conditions for markets with multiple assets and proportional transaction costs. We show that this condition is sufficient for a multi-asset model to be free of arbitrage. We also show that d-dimensional fractional Brownian models are jointly sticky, and we establish a time-change result for joint stickiness.
EDIII‐DENV3 nanospheres drive immature dendritic cells into a mature phenotype in an in vitro model

Domain III of E protein of dengue virus (DENV) is a target for vaccine development. Unfortunately, this protein based platform has low general immunogenicity. To circumvent this problem, the use of an adjuvant‐nanoparticle delivery system to facilitate immunogenicity of soluble DENV‐EDIII protein was investigated. One of the key features of this delivery system is its ability to simultaneously deliver antigens and exert adjuvanticity on specialized immune cells. In this study, N‐trimethyl chitosan (TMC) nanoparticles (NPs) were generated to be used as adjuvant and carrier for soluble E‐domain III of dengue virus serotype 3 (sEDIII‐D3). Using ionotropic gelation, purified sEDIII‐D3 was encapsulated into TMC NPs to form EDIII‐D3 TMC NPs. After optimization, EDIII‐D3 TMC particles exhibited a loading efficiency of 81% and a loading capacity of 41%. The immunogenicity of EDIII‐D3 TMC NPs was tested using monocyte‐derived dendritic cells (MoDCs). It was found that EDIII‐D3 TMC NPs were well taken up by MoDCs. In addition, EDIII‐D3 TMC NP treated MoDCs significantly upregulated maturation markers (CD80, CD83, CD86 and HLA‐DR) and induced secretion of various cytokines and chemokines (IFN‐α, IL‐1β, IL‐6, IL‐2, IL‐12p70, IFN‐γ, IL‐4, IL‐10, IL‐8, MCP‐1, macrophage inflammatory protein‐1β, granulocyte‐colony stimulating factor, granulocyte–macrophage colony‐stimulating factor and IL‐7). These results indicate that EDIII‐D3 TMC NPs are potent immunogens, at least in vitro, with the ability to induce maturation of DCs and highlight the potential use of TMC NPs for enhancing immunogenicity of a non‐replicating dengue vaccine.
Stabilising the Integrity of Snake Venom mRNA Stored under Tropical Field Conditions Expands Research Horizons

Background Snake venoms contain many proteinaceous toxins that can cause severe pathology and mortality in snakebite victims. Interestingly, mRNA encoding such toxins can be recovered directly from venom, although yields are low and quality is unknown. It also remains unclear whether such RNA contains information about toxin isoforms and whether it is representative of mRNA recovered from conventional sources, such as the venom gland. Answering these questions will address the feasibility of using venom-derived RNA for future research relevant to biomedical and antivenom applications. Methodology/Principal Findings Venom was extracted from several species of snake, including both members of the Viperidae and Elapidae, and either lyophilized or immediately added to TRIzol reagent. TRIzol-treated venom was incubated at a range of temperatures (4–37°C) for a range of durations (0–48 hours), followed by subsequent RNA isolation and assessments of RNA quantity and quality. Subsequently, full-length toxin transcripts were targeted for PCR amplification and Sanger sequencing. TRIzol-treated venom yielded total RNA of greater quantity and quality than lyophilized venom, and with quality comparable to venom gland-derived RNA. Full-length sequences from multiple Viperidae and Elapidae toxin families were successfully PCR amplified from TRIzol-treated venom RNA. We demonstrated that venom can be stored in TRIzol for 48 hours at 4–19°C, and 8 hours at 37°C, at minimal cost to RNA quality, and found that venom RNA encoded multiple toxin isoforms that seemed homologous (98–99% identity) to those found in the venom gland. Conclusions/Significance The non-invasive experimental modifications we propose will facilitate the future investigation of venom composition by using venom as an alternative source to venom gland tissue for RNA-based studies, thus obviating the undesirable need to sacrifice snakes for such research purposes. In addition, they expand research horizons to rare, endangered or protected snake species and provide more flexibility to performing fieldwork on venomous snakes in tropical conditions.
Fear of Movement Is Related to Trunk Stiffness in Low Back Pain

Background Psychological features have been related to trunk muscle activation patterns in low back pain (LBP). We hypothesised higher pain-related fear would relate to changes in trunk mechanical properties, such as higher trunk stiffness. Objectives To evaluate the relationship between trunk mechanical properties and psychological features in people with recurrent LBP. Methods The relationship between pain-related fear (Tampa Scale for Kinesiophobia, TSK; Photograph Series of Daily Activities, PHODA-SeV; Fear Avoidance Beliefs Questionnaire, FABQ; Pain Catastrophizing Scale, PCS) and trunk mechanical properties (estimated from the response of the trunk to a sudden sagittal plane forwards or backwards perturbation by unpredictable release of a load) was explored in a case-controlled study of 14 LBP participants. Regression analysis (r 2) tested the linear relationships between pain-related fear and trunk mechanical properties (trunk stiffness and damping). Mechanical properties were also compared with t-tests between groups based on stratification according to high/low scores based on median values for each psychological measure. Results Fear of movement (TSK) was positively associated with trunk stiffness (but not damping) in response to a forward perturbation (r2 = 0.33, P = 0.03), but not backward perturbation (r2 = 0.22, P = 0.09). Other pain-related fear constructs (PHODA-SeV, FABQ, PCS) were not associated with trunk stiffness or damping. Trunk stiffness was greater for individuals with high kinesiophobia (TSK) for forward (P = 0.03) perturbations, and greater with forward perturbation for those with high fear avoidance scores (FABQ-W, P = 0.01). Conclusions Fear of movement is positively (but weakly) associated with trunk stiffness. This provides preliminary support an interaction between biological and psychological features of LBP, suggesting this condition may be best understood if these domains are not considered in isolation.
Feedlot diet roughage level for Hereford cattle exposed to excessive heat load

In Exp. 1, six individually fed Hereford steers were exposed to hot (HOT) or thermoneutral (TNL) environmental conditions (ENV) while being adapted (stepped-up) to a finishing diet by decreasing roughage level from 55 to 10% of the diet DM over 17 d. Only at 10% roughage did heat exposure result in reduced (P<0.05) calculated ME intake (MEI) and measured DMI. In the TNL treatment group, pulse rates increased as MEI and diet energy density increased (P<0.05), whereas in the HOT treatment group, pulse rate tended to decline when MEI declined. Body temperature (BT) of steers increased under both TNL and HOT conditions. In Exp. 2, six individually fed feedlot steers were assigned in a replicated (n = 3) 2 × 3 factorial arrangement of treatments and exposed to HOT or TNL ENV, whereas the diet treatments were a 6% roughage diet fed ad libitum (HE), or 90% of ad libitum (RE), or a 28% roughage diet (HR) fed ad libitum such that MEI approximated the MEI of the RE group. Steers fed HR diets had lower (P<0.05) respiratory rate and BT than HE and RE fed steers. Steers fed RE diets had greater (P<0.05) water intake than HE fed steers when averaged across ENV. Lower BT (P<0.05) of cattle fed RE and HR would indicate MEI prior to exposure to excessive heat load (EHL) influences ability of cattle to cope with subsequent exposure to excessive heat load. Data also indicate that adapting cattle to high energy diets partially contributes to EHL.
Medical costs and utilization in patients with depression treated with adjunctive atypical antipsychotic therapy

Objective To compare total medical costs and utilization over a 12-month period in commercially insured patients receiving FDA-approved adjunctive atypical antipsychotics (aripiprazole, olanzapine, or quetiapine) for depression. Methods A retrospective claims analysis was conducted from 2005–2010 using the PharMetrics database. Subjects were adult commercial health-plan members with depression, identified using International Classification of Diseases codes and followed for 12 months after augmentation with an atypical antipsychotic. Outcomes included total medical costs, hospitalization, and ER visits. Generalized linear models and logistic regression were used to compare the total medical costs and the odds of hospitalization and ER visits between the treatment groups after adjusting for baseline demographic and clinical characteristics. Results A total of 9675 patients with depression were included in the analysis, of which 68.4% were female, with a mean age of 45.2 (±12.0) years. Adjusted 12-month total medical costs were higher for olanzapine ($14,275) and quetiapine ($12,998) compared to aripiprazole ($9,801; P < 0.05 for all comparisons with aripiprazole). When divided into inpatient and outpatient costs, olanzapine and quetiapine had significantly higher adjusted inpatient costs compared to aripiprazole ($6,124 and $4,538 vs $2,976, respectively; P < 0.05 for all comparisons with aripiprazole). Similar results were seen for adjusted outpatient costs. Adjusted odds of hospitalization for olanzapine (odds ratio [OR] = 1.73; 95% CI confidence interval [CI] = 1.42–2.10) and quetiapine (OR = 1.40; 95% CI = 1.21–1.60) were significantly higher than aripiprazole at 12 months. The adjusted odds of an ER visit for olanzapine (OR = 1.40; 95% CI = 1.18–1.65) and quetiapine (OR = 1.62; 95% CI = 1.44–1.81) were also significantly higher compared to aripiprazole at 12 months. Conclusions In commercially insured major depressive disorder patients, olanzapine and quetiapine were associated with higher total medical costs, the difference being primarily attributable to higher inpatient costs. Additionally, olanzapine and quetiapine were associated with significantly higher odds of hospitalization and ER visits compared to aripiprazole.
Flowing on Riemannian Manifold: Domain Adaptation by Shifting Covariance

Domain adaptation has shown promising results in computer vision applications. In this paper, we propose a new unsupervised domain adaptation method called domain adaptation by shifting covariance (DASC) for object recognition without requiring any labeled samples from the target domain. By characterizing samples from each domain as one covariance matrix, the source and target domain are represented into two distinct points residing on a Riemannian manifold. Along the geodesic constructed from the two points, we then interpolate some intermediate points (i.e., covariance matrices), which are used to bridge the two domains. By utilizing the principal components of each covariance matrix, samples from each domain are further projected into intermediate feature spaces, which finally leads to domain-invariant features after the concatenation of these features from intermediate points. In the multiple source domain adaptation task, we also need to effectively integrate different types of features between each pair of source and target domains. We additionally propose an SVM based method to simultaneously learn the optimal target classifier as well as the optimal weights for different source domains. Extensive experiments demonstrate the effectiveness of our method for both single source and multiple source domain adaptation tasks.
EFFECT OF PORE WATER ON THE COMPRESSIVE STRENGTH OF WET CONCRETE

The compressive strength of wet concrete influenced by pore water is investigated in this paper. Pore water pressure induced by compression in the wet concrete affects the mechanical properties of concrete, but the related research is little. The magnitude of pore pressure relates with the volumetric deformation of concrete and the developing velocity of cracks. Based on fracture mechanics, the effects of pore water on the initiation of crack, the development of crack and the strength of wet concrete are analyzed. The results of this investigation indicate that the pore water decreases the friction force which baffles the development of crack and accelerates the damage of concrete, and the pore pressure acts as a wedge to the crack of concrete. The initiation stress of crack and the compressive strength of wet concrete are decreased comparing with the dry sample.
In Vitro and In Vivo Evaluations of PLGA Microspheres Containing Nalmefene

Poor patient compliance, untoward reactions and unstable blood drug levels after the bolus administration are impeding the pharmacotherapy for insobriety. A long-acting preparation may address these limitations. The aim of this paper was to further investigate the in vitro characteristics and in vivo performances of nalmefene microspheres. Nalmefene was blended with poly (lactide-co-glycolide) (PLGA) to prepare the target microspheres by an O/O emulsification solvent evaporation method. The prepared microspheres exhibited a controlled release profile of nalmefene in vitro over 4 weeks, which was well fitted with a first-order model. In vitro degradation study showed that the drug release in vitro was dominated by both drug diffusion and polymer degradation mechanisms. Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats. The in vivo pharmacokinetics profile was well correlated with the in vitro drug release. Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats. These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.
Standoff spectroscopy via remote generation of a backward-propagating laser beam

In an earlier publication we demonstrated that by using pairs of pulses of different colors (e.g., red and blue) it is possible to excite a dilute ensemble of molecules such that lasing and/or gain-swept superradiance is realized in a direction toward the observer. This approach is a conceptual step toward spectroscopic probing at a distance, also known as standoff spectroscopy. In the present paper, we propose a related but simpler approach on the basis of the backward-directed lasing in optically excited dominant constituents of plain air, N2 and O2. This technique relies on the remote generation of a weakly ionized plasma channel through filamentation of an ultraintense femtosecond laser pulse. Subsequent application of an energetic nanosecond pulse or series of pulses boosts the plasma density in the seed channel via avalanche ionization. Depending on the spectral and temporal content of the driving pulses, a transient population inversion is established in either nitrogen- or oxygen-ionized molecules, thus enabling a transient gain for an optical field propagating toward the observer. This technique results in the generation of a strong, coherent, counterpropagating optical probe pulse. Such a probe, combined with a wavelength-tunable laser signal(s) propagating in the forward direction, provides a tool for various remote-sensing applications. The proposed technique can be enhanced by combining it with the gain-swept excitation approach as well as with beam shaping and adaptive optics techniques.