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Rayleigh scattering enhanced nanoparticle-doped optical fibers, for distributed sensing applications, is a new technology that offers unique advantages to optical fiber community. However, the existing fabrication technology, based on in situ grown alkaline earth nanoparticles, is restricted to few compositions and exhibit a great dependence on many experimental conditions. Moreover, there is still several uncertainties about the effect of drawing process on the nanoparticle characteristics and its influence on the scattering enhancement and the induced optical loss. In this work, we shed light on all these issues that prevent the progress in the field and demonstrate the suitability of doping optical fibers with YPO4 nanocrystals for developing tunable Rayleigh scattering enhanced nanoparticle-doped optical fibers. An exhaustive 3D microstructural study reveals that their features are closely linked to the fiber drawing process, which allow the size and shape engineering at the nanoscale. In particular, the YPO4 nanocrystals preserve their features to a large extent when the optical fibers are drawn below 1950 °C, which allows obtaining homogeneous nanocrystal features and optical performance. Fabricated fibers exhibit a tunable enhanced backscattering in the range of 15.3–54.3 dB, with respect to a SMF-28 fiber, and two-way optical losses in the range 0.3–160.7 dB/m, revealed by Optical Backscatter Reflectometry (OBR) measurements. This allows sensing lengths from 0.3 m up to more than 58 m. The present work suggests a bright future of YPO4 nanocrystals for distributed sensing field and open a new gate towards the incorporation of other rare-earth orthophosphate (REPO4) nanocrystals with pre-defined characteristics that will overcome the limitations of the current in situ grown alkaline earth-based technology. [ABSTRACT FROM AUTHOR]

Background: Combination therapy offers a promising option to enhance efficacy and prevent resistance. A comprehensive and quantitative assessment of the last-resort combination of ceftazidime/avibactam and tigecycline is not available., Objective: This study systematically investigated the pharmacodynamic interaction between ceftazidime/avibactam and tigecycline in clinical and isogenic Escherichia coli and Klebsiella pneumoniae strains harbouring genes that encode various carbapenemases or ESBLs., Methods: An adaptive in vitro 'dynamic' checkerboard design and pharmacometric modelling were employed for the evaluation of pharmacodynamic interactions in fifteen bacterial isolates. Additionally, time-kill assays and metabolomic analyses were used to provide mechanistic insights., Results: Antagonistic drug interactions between ceftazidime/avibactam and tigecycline were identified in the majority of tested strains. Time-kill assays confirmed antagonistic interactions, with tigecycline limiting ceftazidime/avibactam total killing. Metabolomic analyses of mono and combined drug exposure to bacteria revealed matching metabolomes in tigecycline alone and the combination with ceftazidime/avibactam, corroborating the identified antagonism between these drugs., Conclusions: Our study reveals that the antagonistic interaction between ceftazidime/avibactam and tigecycline can undermine ceftazidime/avibactam's efficacy, suggesting limited clinical benefit in combining these antibiotics. Therefore, further research is encouraged to explore this and alternative combinations or approaches that may offer better clinical outcomes., Competing Interests: Declaration of competing interest We declare no conflicts of interest related to this study., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The objective of this study was to examine the influence of different environmental factors on ATP luminometry measurements of feeding equipment and to investigate associations with health of preweaning calves and the levels of ATP identified through luminometry. On 50 commercial dairy farms in Quebec, Canada, ATP luminometry measurements (in relative light units, RLU) were obtained using the direct swabbing technique with Hygiena UltraSnap swabs and a liquid rinsing technique with the same swab for automatic milk feeders (AMF), bottles, buckets, esophageal tube feeders (ET), milk replacer, nipples, and water. During this visit, environmental factors (including temperature, air draft, humidity, ammonia, and bacterial count) were collected, and a clinical examination (including respiratory score and fecal score) was performed for all preweaning calves present at the farm. This process was repeated 4 times in a year, leading to collection of luminometer results, environmental parameters, and overall health of calves for each season per farm. Overall, a difference in luminometer results was seen between the different periods sampled for all feeding equipment (except the ET), milk replacer, and water, showing higher RLU values in spring and summer and lower values in autumn and winter. When comparing RLU measurements with environmental factors, only a low to negligible correlation could be found. When feeding equipment was classified as not contaminated or contaminated based on previously described cutoff values, a good agreement within a farm for the different seasons was noticed only for nipples (Gwet's agreement AC1 = 0.64), with a poor to moderate agreement for other feeding equipment. Regarding the different models of nipples, Peach Teat nipples showed higher RLU values compared with Merrick's nipples. An association was seen between the proportion of preweaning calves suffering from diarrhea on the farm and the contamination of AMF based on ATP luminometry (logistic regression estimate = 0.52). For other feeding equipment, milk replacer, and water, no significant associations were found. This study showed that ATP luminometry measurements of feeding equipment from preweaning calves are susceptible to seasonality and type of nipple. Thus, these factors should be taken into consideration when interpreting results. Additionally, an association could be made between diarrhea in preweaning calves and the contamination of AMF based on ATP luminometry, showing the potential clinical importance of this on-farm hygiene assessment tool., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

We report the femtosecond laser writing of meter-long optical waveguides inscribed through the coating of specifically designed optical fibers. In order to improve the material photosensitivity and to ensure non-guiding optical fibers for subsequent laser processing of the waveguiding core, a depressed refractive index core design is implemented by co-doping a large portion of the optical fiber with germanium oxide and fluorine. The enhanced photosensitivity provided by further deuterium loading these fibers allows laser-writing of large refractive index contrast waveguides over wide cross sections. To mitigate the formation of photoinduced color centers causing high propagation losses in the photo-written waveguides, thermal annealing up to 400°C is performed on polyimide-coated laser-written fibers. Although the refractive index contrast decreases, the propagation losses are drastically reduced down to 0.08 dB/cm at 900nm allowing a robust single-mode guiding from visible to near infrared. Our results pave the way towards the development of a new generation of optical fibers and photonic components with arbitrarily complex designs.

Background: The main antibiotics used against Helicobacter pylori have been chosen empirically over time, with few preclinical studies to provide support. The rise in resistance to some of these antibiotics is prompting a reassessment of their use. This work aimed to evaluate the in vitro efficacy of 2 × 2 combinations of the most widely used antibiotics against H. pylori., Materials and Methods: J99 reference strains and 19 clinical isolates of H. pylori with various antibiotic resistance phenotypes were used. Minimum inhibitory concentrations were carried out using the microdilution method in 96-well plates. The activity of 15 possible combinations of two antibiotics including amoxicillin, clarithromycin (CLA), levofloxacin, rifampicin, tetracycline, and metronidazole was determined for all strains by the checkerboard method. A mean fractional inhibitory concentration index (FIC mean ) was calculated for each combination and strain and the type of pharmacodynamic interaction was considered as synergic if FIC mean  ≤ 0.5, additive if 0.5 < FIC mean  ≤ 1, indifferent if 1 < FIC mean  < 4 or antagonistic if FIC mean  ≥ 4., Results: Most of the 285 pharmacodynamic interactions tested with clinical strains were close to additivity (average FIC mean  = 0.89 [0.38-1.28]). No interaction was found to be antagonistic. When two antibiotics to which a strain was resistant were combined, the concentrations required to inhibit bacterial growth were higher than their respective breakpoints., Conclusion: The present results have shown that in vitro, the different antibiotics used in therapeutics have additive effects. The addition of the effects of two antibiotics to which a strain was resistant was not sufficient to inhibit bacterial growth. In probabilistic treatment, the choice of antibiotics to combine should therefore be based on the local epidemiology of resistance, and on susceptibility testing in the case of CLA therapy, so that at least one antibiotic to which the strain is susceptible is used., (© 2024 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Importance: Mechanistic understanding of pharmacodynamic interactions is key for the development of rational antibiotic combination therapies to increase efficacy and suppress the development of resistances. Potent tools to provide those insights into pharmacodynamic drug interactions are semi-mechanistic modeling and simulation techniques. This study uses those techniques to provide a detailed understanding with regard to the direction and strength of the synergy of ceftazidime-avibactam and ceftazidime-fosfomycin in a clinical Escherichia coli isolate expressing extended spectrum beta-lactamase (CTX-M-15 and TEM-4) and carbapenemase (OXA-244) genes. Enhanced killing effects in combination were identified as a driver of the synergy and were translated from static time-kill experiments into the dynamic hollow fiber infection model. These findings in combination with a suppression of the emergence of resistance in combination emphasize a potential clinical benefit with regard to increased efficacy or to allow for dose reductions with maintained effect sizes to avoid toxicity., Competing Interests: The authors declare no conflict of interest.

The objective of this study was to describe the cleaning practices currently used for preweaning calves on dairy farms in Quebec, Canada. In addition, contamination of feeding equipment for preweaning calves was described using ATP (expressed as relative light units, RLU), visual assessment, and bacteriological analysis. A questionnaire was administered on 50 commercial dairy farms in Quebec, Canada, regarding the self-reported cleaning protocol used for feeding equipment of preweaning calves. During the visit, a visual score was given to the feeding equipment available at the farm. Afterward, ATP luminometry measurements were obtained using Hygiene UltraSnap and MicroSnap swabs (Hygiene, Camarillo, CA), and the liquid rinsing technique for buckets, nipples, bottles, esophageal tube feeders (ET), the tube of automatic milk feeders (AMF), water samples, and milk replacer. An additional direct swabbing technique was performed on buckets and nipples. The fluid retrieved from the liquid rinsing technique was also used to determine the total bacterial count (TBC) and total coliform count. Based on the bacteriological analysis, optimal RLU cutoff values to determine contamination were obtained. The median (interquartile range) luminometer measurements using the UltraSnap and direct technique for buckets and nipples were 2,082 (348-7,410) and 3,462 (462-7,518) RLU, respectively; and, using the liquid technique for bottles, ET, AMF, water, and milk replacer were 43 (4-974), 15 (4-121), 301 (137-1,323), 190 (71-358), and 94 (38-218) RLU, respectively. Overall, for all equipment and both techniques used, higher RLU values were seen in UltraSnap samples compared with MicroSnap samples. Additionally, for buckets and nipples, higher RLU values were obtained for the direct swabbing method compared with the liquid sampling method for both swabs used. No differences in the level of contamination were seen between the different feeding equipment used within a farm. Overall, a higher correlation with bacteriological results was noticed for ATP luminometry compared with the visual score, with a high correlation for nipples and bottles using the UltraSnap and liquid technique. Based on the classification of "contaminated" (TBC ≥100,000 cfu/mL) or "not contaminated" (TBC <100,000 cfu/mL), optimal ATP luminometer cutoff values for buckets, nipples, bottles, AMF, water, and milk replacer were 798, 388, 469, 282, 1,432, and 93 RLU, respectively. No clear association was found between ATP measurements and the self-reported cleaning protocol. This study gave new insights into the current cleaning procedures and contamination of feeding equipment for preweaning calves on dairy farms in Quebec. In addition, ATP luminometry cutoff values could help benchmark farms regarding cleaning practices and provide customized advice, improving the overall hygiene management, and thus the health, of preweaning calves on dairy farms., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

A double ampC (AmpC G183D ) and ampD (AmpD H157Y ) genes mutations have been identified by whole genome sequencing in a Pseudomonas aeruginosa (PaS) that became resistant (PaR) in a patient treated by ceftolozane/tazobactam (C/T). To precisely characterize the respective contributions of these mutations on the decreased susceptibility to C/T and on the parallel increased susceptibility to imipenem (IMI), mutants were generated by homologous recombination in PAO1 reference strain (PAO1- AmpC G183D , PAO1-AmpD H157Y , PAO1-AmpC G183D /AmpD H157Y ) and in PaR (PaR-AmpC PaS /AmpD PaS ). Sequential time-kill curve experiments were conducted on all strains and analyzed by semi-mechanistic PKPD modeling. A PKPD model with adaptation successfully described the data, allowing discrimination between initial and time-related (adaptive resistance) effects of mutations. With PAO1 and mutant-derived strains, initial EC 50 values increased by 1.4, 4.1, and 29-fold after AmpC G183D , AmpD H157Y and AmpC G183D /AmpD H157Y mutations, respectively. EC 50 values were increased by 320, 12.4, and 55-fold at the end of the 2 nd experiment. EC 50 of PAO1-AmpC G183D /AmpD H157Y was higher than that of single mutants at any time of the experiments. Within the PaR clinical background, reversal of AmpC G183D , and AmpD H157Y mutations led to an important decrease of EC 50 value, from 80.5 mg/L to 6.77 mg/L for PaR and PaR-AmpC PaS /AmpD PaS , respectively. The effect of mutations on IMI susceptibility mainly showed that the AmpC G183D mutation prevented the emergence of adaptive resistance. The model successfully described the separate and combined effect of AmpC G183D and AmpD H157Y mutations against C/T and IMI, allowing discrimination and quantification of the initial and time-related effects of mutations. This method could be reproduced in clinical strains to decipher complex resistance mechanisms., Competing Interests: The authors declare no conflict of interest.

In contrast to the checkerboard method, bactericidal experiments [time-kill curves (TKCs)] allow an assessment of pharmacodynamic (PD) interactions over time. However, TKCs in combination pose interpretation problems. The objective of this study was to characterize the PD interaction over time between ceftazidime/avibactam (CZA) and colistin (CST) using TKC against four multidrug-resistant Klebsiella pneumoniae susceptible to both antibiotics and expressing a widespread carbapenemase determinant KPC-3. In vitro TKCs were performed and analyzed using pharmacokinetic/pharmacodynamic (PKPD) modeling. The general pharmacodynamic interaction model was used to characterize PD interactions between drugs. The 95% confidence intervals (95%CIs) of the expected additivity and of the observed interaction were built using parametric bootstraps and compared to evaluate the in vitro PD interaction over time. Further simulations were conducted to investigate the effect of the combination at varying concentrations typically observed in patients. Regrowth was observed in TKCs at high concentrations of drugs alone [from 4 to 32× minimum inhibitory concentrations (MIC)], while the combination systematically prevented the regrowth at concentrations close to the MIC. Significant synergy or antagonism were observed under specific conditions but overall 95%CIs overlapped widely over time indicating an additive interaction between antibiotics. Moreover, simulations of typical PK profile at standard dosages indicated that the interaction should be additive in clinical conditions. The nature of the PD interaction varied with time and concentration in TKC. Against the four K. pneumoniae isolates, the bactericidal effect of CZA + CST combination was predicted to be additive and to prevent the emergence of resistance at clinical concentrations., Competing Interests: The authors declare no conflict of interest.

Background: Combination therapy can increase efficacy of antibiotics and prevent emergence of resistance. Ceftazidime/avibactam and fosfomycin may be empirically combined for this purpose, but a systematic and quantitative evaluation of this combination is needed., Objectives: In this study, a systematic analysis of the pharmacodynamic interactions of ceftazidime/avibactam and fosfomycin in clinical and isogenic Escherichia coli strains carrying genes coding for several carbapenemases or ESBLs was performed and pharmacodynamic interactions were quantified by modelling and simulations., Methods: Pharmacodynamic interactions were evaluated in 'dynamic' chequerboard experiments with quantification of viable bacteria in eight isogenic and six clinical E. coli strains. Additionally, supplemental time-kill experiments were performed and genomic analyses were conducted on representative fosfomycin-resistant subpopulations. Models were fitted to all data using R and NONMEM®., Results: Synergistic drug interactions were identified for 67% of the clinical and 75% of the isogenic isolates with a mean EC50 reduction of >50%. Time-kill experiments confirmed the interactions and modelling quantified EC50 reductions up to 97% in combination and synergy prevented regrowth of bacteria by enhanced killing effects. In 9 out of 12 fosfomycin-resistant mutants, genomic analyses identified previously reported mutations., Conclusions: The broad synergistic in vitro activity of ceftazidime/avibactam and fosfomycin confirms the potential of the application of this drug combination in clinics. The substantial reduction of the EC50 in combination may allow use of lower doses or treatment of organisms with higher MIC values and encourage further research translating these findings into the clinical setting., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this cross-sectional study was to standardize a reliable and repeatable swabbing technique using ATP luminometry (light emission proportional to the amount of ATP with result provided in relative light units [RLU]) to describe the cleanliness of various feeding equipment used for preweaning calves in dairy farms. A total of 7 Québec commercial dairy herds were selected conveniently. Following visual hygiene scoring, the cleanliness of every available piece of feeding equipment was assessed using direct surface swabbing for buckets and nipples with Hygiena UltraSnap swabs. A liquid rinsing technique was used for esophageal feeders, bottles, and automatic milk feeders (AMF) with UltraSnap, AquaSnap, and MicroSnap swabs. To validate direct swabbing technique of buckets, a stage within and between operators was realized, as well as a conventional bacterial culture. A total of 519 swab samples were obtained from 201 pieces of equipment. The median (interquartile range) contamination in RLU for a bottle, esophageal feeder, AMF, bucket and nipple was 2 (1;6), 2 (0;12), 52 (19;269), 886 (128;7,230) and 899 (142;6,928), respectively. The direct swabbing technique, which consists in swabbing directly the surface of an equipment, showed excellent correlation for intrarater reliability (intraclass correlation (ICC) = 0.93; 95% CI: 0.88-0.96). The interoperator (2 sessions with 3 different operators) reliability also showed high correlation (ICC = 0.88; 95% CI: 0.78-0.94 for the first session, and ICC = 0.89; 95% CI: 0.79-0.95 for the second session). Luminometer values were positively associated with the visual score of esophageal feeders, AMF and buckets. A positive correlation between bacterial culture and direct swabbing of buckets was also found for the UltraSnap (r s = 0.653; 95% CI: 0.283-0.873; P = 0.0003) and MicroSnap (r s = 0.569, 95% CI: 0.309-0.765; P = 0.002). This study describes a standardized and practical on-farm swabbing technique for assessing the hygienic status of feeding equipment by luminometry, which can be integrated in the investigation of preweaning dairy calves problems., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

An in-depth characterization of nanoparticle-doped optical fibers is crucial to understand the potential new functionalities of the engineered glass and thus their applicability fields. The high temperatures of the manufacturing process strongly affect the nanoparticle features, and therefore, their analysis is necessary after fiber drawing. However, the difficulties associated with the use of atomic resolution microscopies to analyze the nanoparticle features in the fiber core, mainly related to sample preparation and expensive costs, usually prevent their study. In this work, we overcome some of those limitations and demonstrate, for the first time, the suitability of structurally and microstructurally studying in detail nanocrystals contained in a fiber core of ∼10 μm by combining confocal Raman microscopy, Rayleigh light-scattering microscopy, and scanning electron microscopy (SEM). A thorough study of cubic-shaped and rod-shaped YPO 4 nanocrystals contained in optical fibers reveals their crystallization in tetragonal (t) and monoclinic (m) structures, respectively. The symmetric (ν 1 ) and asymmetric stretching (ν 3 ) Raman modes display a different and remarkable red shift as particle size decreases in both types of nanocrystals, which in the case of the cubic-shaped nanocrystals is fitted to an exponential function along with a Raman peak broadening. Moreover, their Raman dependence vs temperature is evaluated up to 600 °C, observing a phonon softening that follows a linear behavior, which is discussed in detail. These findings add new insights to pure m-YPO 4 , which was unknown to date, and the REPO 4 family and open up new avenues that can be extrapolated to other nanostructures incorporated into optical fiber cores, which will advance progress in the field of nanoparticle-doped optical fibers.