Background. The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens ...is a major challenge for clinicians. Methods. In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results. The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio OR: 7.17; 95% confidence interval CI: 1.65–31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61–10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02–1.07; P < .001). Postantibiogram therapy with a combination of tigecycline, colistin, and meropenem was associated with lower mortality (OR: 0.11; 95% CI: .02–.69; P = .01). Conclusions. KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.
Laser ultrasonics (LU) is a non-contact and non-destructive method with a high data acquisition rate, making it a promising candidate for in-situ monitoring of defects in different additive ...manufacturing (AM) processes, including laser powder bed fusion (LPBF) and directed energy deposition, as well as final part inspection. In order to see the effect of various artificial defect types on an LU sub-surface reconstruction, AlSi10Mg samples with side through-holes, as well as Ti6Al4V samples with bottom blind holes and trapped powder were printed using LPBF, and then ultrasound B-scans of the samples were obtained using an LU system. The resulting scan data was processed using a custom frequency domain phase shift migration (PSM) algorithm, to reconstruct the defects and their locations. Novel ways of pre-processing the B-scan, used as an input to PSM, and taking advantage of its frequency representation, are demonstrated. Newton’s method was used to find a stationary phase approximation, used to account in the frequency domain for the fixed offset emitter-receiver arrangement within the PSM calculation. The Newton’s method calculation time was reduced by 33%, by using an approximation of the phase function to find an initial guess. The smallest defects that were detected using this method were in the size range between 200 to 300μm for the bottom hole defects, using an 8 ns laser pulse duration. The effect of the laser on the surface of a part being built, and the challenges and further work needed to integrate LU in a LPBF machine for in-situ inspection are discussed.
•A laser ultrasound (LU) setup and algorithm for detecting defects in LPBF parts.•Image reconstructions showing a detection resolution of 300 to 200μm.•Algorithm to account in frequency domain for constant generation-receiver offset.•Method of filtering the ultrasonic B-scan data to account for high surface roughness.•Method for filtering signals due to reflections from the part’s surfaces being built.•Measurements done in samples with no-up skin to simulate in-situ measurements.
Treating severe infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) is one of the most important challenges for clinicians worldwide, partly because resistance may remain ...unrecognized until identification of the causative agent and/or antimicrobial susceptibility testing (AST). Recently, some novel rapid test for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with bloodstream infections (BSIs) have become available.
The objective of this narrative review is to discuss the advantages and limitations of different rapid tests for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with BSI, as well as the available evidence on their possible role to improve therapeutic decisions and antimicrobial stewardship.
Inductive PubMed search for publications relevant to the topic.
The present review is structured in the following way: (a) rapid tests on positive blood cultures; (b) rapid tests directly on whole blood; (c) therapeutic implications.
Novel molecular and phenotypic rapid tests for identification and AST show the potential for favourably influencing patients' outcomes and results of antimicrobial stewardship interventions by reducing both the time to effective treatment and the misuse of antibiotics, although the interpretation about their impact on actual therapeutic decisions and patients' outcomes is still complex. Factors such as feasibility and personnel availability, as well as the detailed knowledge of the local microbiological epidemiology, need to be considered very carefully when implementing novel rapid tests in laboratory workflows and algorithms. Providing high-level, comparable evidence on the clinical impact of rapid identification and AST is becoming of paramount importance for MDR-GNB infections, since in the near future rapid identification of specific resistance mechanisms could be crucial for guiding rapid, effective, and targeted therapy against specific resistance mechanisms.
In this paper we study general transportation problems in
R
n
, in which
m
different goods are moved simultaneously. The initial and final positions of the goods are prescribed by measures
μ
-
,
μ
+
...on
R
n
with values in
R
m
. When the measures are finite atomic, a discrete transportation network is a measure
T
on
R
n
with values in
R
n
×
m
represented by an oriented graph
G
in
R
n
whose edges carry multiplicities in
R
m
. The constraint is encoded in the relation
div
(
T
)
=
μ
-
-
μ
+
. The cost of the discrete transportation
T
is obtained integrating on
G
a general function
C
:
R
m
→
R
of the multiplicity. When the initial data
μ
-
,
μ
+
are arbitrary (possibly diffuse) measures, the cost of a transportation network between them is computed by relaxation of the functional on graphs mentioned above. Our main result establishes the existence of cost-minimizing transportation networks for arbitrary data
μ
-
,
μ
+
. Furthermore, under additional assumptions on the cost integrand
C
, we prove the existence of transportation networks with finite cost and the stability of the minimizers with respect to variations of the given data. Finally, we provide an explicit integral representation formula for the cost of rectifiable transportation networks, and we characterize the costs such that every transportation network with finite cost is rectifiable.
Scanning strategies can significantly affect temperature distribution and location-specific variation of solidification microstructure in laser-directed energy deposition by powder-feeding (LDED-PF). ...In this paper, a physics-based analytical model of multi-track LDED-PF is developed to rapidly predict the temperature field of cuboidal geometries under four different scanning strategies: bidirectional, unidirectional, inward spiral, and S-pattern. Based on 2D thermal models, a new universal algorithm is developed to predict the geometrical profile of the overlapping beads, applied to all scanning strategies. The effects of four scanning strategies on the temperature field, geometrical profile, and microstructural behavior are investigated and tested. The linkages between the process and solidification microstructure are revealed and rationalized through temperature simulations and microstructural characterization. The developed model is tested for multi-track deposition of near-β titanium (Ti-5Al-5 V-5Mo-3Cr) alloy at different laser powers, scanning speeds, and step-over distances under different scanning strategies. The solidification maps are established for the alloy, and the microstructural evolution of columnar to equiaxed transition (CET) is predicted. The results indicate that the model can ideally predict the deposition dimensions, temperature field, and solidification microstructure. This modeling methodology is applicable to other metallic materials, and it can be used to manipulate and engineer the location-specific variation of solidification microstructure.
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The avian retina is composed of different types of photoreceptors responsible for image and non-image forming tasks: the visual photoreceptor cells (cones and rods), the melanopsin-expressing ...intrinsically photoresponsive retinal ganglion cells (ipRGCs) and horizontal cells. Furthermore, the non-visual opsins Opn3 (encephalopsin/panaopsin) and Opn5 (neuropsin) have been shown to be expressed in the vertebrate inner retina, responding to blue (BL) and UV light, respectively. Here we investigated the expression and localization of Opn3 and Opn5 in the developing chick retina at different embryonic days (E) as well as in primary cultures of retinal Müller glial cells (MCs). Opn3 and Opn5 mRNAs and proteins appeared as early as E10 although traces of Opn3- and Opn5-like proteins were seen earlier by E7 in the forming RGC layer and in glial cells extending throughout the developing nuclear layer. Later on, at postnatal days 1-10 (PN1-10) a significant expression of Opn3 was observed in inner retinal cells and processes in plexiform layers, together with expression of the glial markers glutamine synthetase (GS) and the glial fibrillary acidic protein (GFAP). Opn3 and Opn5 were found to be expressed in primary MC cultures prepared at E8 and kept for 2 weeks. In addition, significant effects of BL exposure on Opn3 expression and subcellular localization were observed in MCs as BL significantly increased its levels and modified its nuclear location when compared with dark controls, through a mechanism dependent on protein synthesis. More importantly, a subpopulation of MCs responded to brief BL pulses by increasing intracellular Ca
levels; whereas light-responses were completely abolished with the retinal bleacher hydroxylamine pretreatment. Taken together, our findings show that these two opsins are expressed in inner retinal cells and MCs of the chicken retina at early developmental phases and remain expressed in the mature retina at PN days. In addition, the novel photic responses seen in MCs may suggest another important role for the glia in retinal physiology.
The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality ...of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case–control–control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals.
One of the challenges in directed energy deposition via powder feeding (DED-PF) is the powder stream divergence that results in low catchment efficiency (i.e., the fraction of particles added to the ...melt pool). This article introduces a new ultrasound-based powder focusing method referred to as ultrasound particle lensing (UPL), tailored for powder used in DED-PF. The method uses an ultrasound phased array to produce a small volume of high-intensity ultrasound with the required period averaged sound intensity profile. UPL was used to acoustically focus streams of Ti64 and SS 316L particles with an average size of 89μm and a particle speed of 0.6 m/s, exiting from a DED-PF nozzle analog. The e−1 powder stream widths downstream of the resulting force fields for both materials were reduced by 30%. The experimental results closely match Lagrangian and Eulerian simulations of the process. This novel setup offers the possibility of fast control of the powder stream divergence angle and effective diameter in the process zone during the DED-PF process. This will in turn improve the feature resolution and catchment efficiency of the process.
•Simulation and experiments on new powder stream focusing method are presented.•The method is used to focus metal powder using an ultrasound phased array.•A new particle stream model is used to model particle stream/force field interaction.
•Artemisinin extraction by supercritical fluid extraction was evaluated.•Co-solvent addition increased the extraction but decreased the artemisinin content.•Supercritical fluid extraction is ...technically and economically advantageous.•Cost of manufacturing was mainly affected by raw material acquisition cost.•Reducing cost of raw material is necessary to make the process economically viable.
Artemisia annua L. is the main artemisinin source, a sesquiterpene lactone used in the treatment against cancer and malaria, whose demand is high and the costs involving its production must be feasible. The main objective of the present work was to define a industrially and economically viable technology to obtain artemisinin. The experimental conditions of temperature, pressure and co-solvent use for obtaining extracts enriched in artemisinin by supercritical fluid extraction (SFE) were investigated, and an economic evaluation of the SFE was performed in comparison with the conventional extraction using ethanol. The techno-economic analysis showed that among the conditions evaluated in the present study, SFE at 60 °C and 250 bar, without co-solvent, was the most promising production condition. Nevertheless, for the commercial viability of the arteminisin extraction using SFE it is indicated to use A. annua rigorously selected, and to reduce costs of raw material.
The effects of multiple irrigation regimes on the relationships among tree water status, vegetative growth and productivity within a super-high-density (SHD) “Arbequina” olive grove (1950 tree/ha) ...were studied for three seasons (2008–2010). Five different irrigation levels calculated as percentage of crop irrigation requirement using FAO procedures (Allen et al. in Crop evapotranspiration. Guidelines for computing crop water requirements. Irrigation and drainage paper 56. FAO, Rome,
1998
) were imposed during the growing season. Periodically during the growing season, daytime stem water potential (
Ψ
STEM
), inflorescences per branch, fruits per inflorescence and shoot absolute growth rate were measured. Crop yield, fruit average fresh weight and oil polyphenol content were measured after harvest. The midday
Ψ
STEM
ranged from −7 to −1.5 MPa and correlated well enough with yield efficiency, crop density and fruit fresh weight to demonstrate its utility as a precise method for determining water status in SHD olive orchards. The relationships between midday
Ψ
STEM
and the horticultural parameters suggest maintaining
Ψ
STEM
values between −3.5 and −2.5 MPa is optimal for moderate annual yields of good quality oil. Values below −3.5 MPa reduced current season productivity, while values over −2.5 MPa were less effective in increasing productivity, reduced oil quality and produced excessive crop set that strongly affected vegetative growth and fruit production the following season. On the basis of the result given here, irrigation scheduling in the new SHD orchards should be planned on a 2-year basis and corrected annually based on crop load. Collectively, these results suggest that deficit irrigation management is a viable strategy for SHD olive orchards.
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