Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration. We have focused on developing novel DTIC salt/cocrystal forms with enhanced solubility and dissolution behaviors to overcome or minimize this undesirable biopharmaceutical profile. By cocrystallization techniques, two salts, two cocrystals, and one salt-cocrystal have been successfully prepared through reactions with aliphatic carboxylic acids. A detailed structural study of these new multicomponent crystals was conducted using X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Most DTIC crystal forms reported display substantial enhancements in solubility (up to 19-fold), with faster intrinsic dissolution rates (from 1.3 to 22-fold), contributing positively to reducing the photodegradation of DTIC in solution. These findings reinforce the potential of these new solid forms to enhance the limited DTIC biopharmaceutical profile.

Expanding the Phenotypic Spectrum of Pathogenic KIAA0586 Variants: From Joubert Syndrome to Hydrolethalus Syndrome.

KIAA0586 variants have been associated with a wide range of ciliopathies, mainly Joubert syndrome (JS, OMIM #616490) and short-rib thoracic dysplasia syndrome (SRTD, OMIM #616546). However, the hypothesis that this gene is involved with hydrolethalus syndrome (HSL, OMIM #614120) and orofaciodigital syndrome IV (OMIM #258860) has already been raised. Ciliopathies' clinical features are often overlapped despite differing in phenotype severity. Besides KIAA0586, HYLS1 and KIF7 are also known for being causative of ciliopathies, indicating that all three genes may have similar or converging genomic pathways. Overall, the genotypic and phenotypic spectrum of ciliopathies becomes wider and conflicting while more and more new variants are added to this group of disorders' molecular pot. In this case report we discuss the first Brazilian individual clinically diagnosed with hydrolethalus syndrome and molecular findings that demonstrate the role of KIAA0586 as a causative gene of a group of genetic disorders. Also, recent reports on individuals with intronic and exonic variants combined leading to ciliopathies support our patient's molecular diagnosis. At the same time, we discuss variable expressivity and overlapping features in ciliopathies.

First Attempts of the Use of 195Pt NMR of Phenylbenzothiazole Complexes as Spectroscopic Technique for the Cancer Diagnosis.

Platinum complexes have been studied for cancer treatment for several decades. Furthermore, another important platinum characteristic is related to its chemical shifts, in which some studies have shown that the 195Pt chemical shifts are very sensitive to the environment, coordination sphere, and oxidation state. Based on this relevant feature, Pt complexes can be proposed as potential probes for NMR spectroscopy, as the chemical shifts values will be different in different tissues (healthy and damaged) Therefore, in this paper, the main goal was to investigate the behavior of Pt chemical shifts in the different environments. Calculations were carried out in vacuum, implicit solvent, and inside the active site of P13K enzyme, which is related with breast cancer, using the density functional theory (DFT) method. Moreover, the investigation of platinum complexes with a selective moiety can contribute to early cancer diagnosis. Accordingly, the Pt complexes selected for this study presented a selective moiety, the 2-(4'aminophenyl)benzothiazole derivative. More specifically, two Pt complexes were used herein: One containing chlorine ligands and one containing water in place of chlorine. Some studies have shown that platinum complexes coordinated to chlorine atoms may suffer hydrolyses inside the cell due to the low chloride ion concentration. Thus, the same calculations were performed for both complexes. The results showed that both complexes presented different chemical shift values in the different proposed environments. Therefore, this paper shows that platinum complexes can be a potential probe in biological systems, and they should be studied not only for cancer treatment, but also for diagnosis.

Full three-dimensional isotropic carpet cloak designed by quasi-conformal transformation optics.

A fully three-dimensional carpet cloak presenting invisibility in all viewing angles is theoretically demonstrated. The design is developed using transformation optics and three-dimensional quasi-conformal mapping. Parametrization strategy and numerical optimization of the coordinate transformation deploying a quasi-Newton method is applied. A discussion about the minimum achievable anisotropy in the 3D transformation optics is presented. The method allows to reduce the anisotropy in the cloak and an isotropic medium could be considered. Numerical simulations confirm the strategy employed enabling the design of an isotropic reflectionless broadband carpet cloak independently of the incident light direction and polarization.

Three-dimensional quasi-conformal transformation optics through numerical optimization.

In this paper we demonstrate the possibility to achieve 3-dimensional quasi-conformal transformation optics through parametrization and numerical optimization without using sliding boundary conditions. The proposed technique, which uses a quasi-Newton method, is validated in two cylindrical waveguide bends as design examples. Our results indicate an arbitrarily small average anisotropy can be achieved in 3D transformation optics as the number of degrees of freedom provided by the parametrization was increased. The waveguide simulations confirm modal preservation when the residual anisotropy is neglected.

Structure and stability of neutral Al-Mg nanoclusters up to 55 atoms.

The geometries of aluminum-magnesium nanoalloys are explored using a genetic algorithm applied to the Gupta potential function and tuned to search for the 10 lowest energy minima for each cluster size and composition. Each structure is re-optimized using density functional theory calculations, allowing both a classical and quantum analysis of the system. Average binding energies, excess energies and HOMO-LUMO gaps are calculated. Differences between classical and quantum descriptions are discussed. The results reveal structures that are particularly stable, and a discussion on magic numbers of valence electrons is presented.

Contribution of Meat Inspection to the surveillance of poultry health and welfare in the European Union.

In the European Union, Meat Inspection (MI) aims to protect public health by ensuring that minimal hazardous material enters in the food chain. It also contributes to the detection and monitoring of animal diseases and welfare problems but its utility for animal surveillance has been assessed partially for some diseases only. Using the example of poultry production, we propose a complete assessment of MI as a health surveillance system. MI allows a long-term syndromic surveillance of poultry health but its contribution is lowered by a lack of data standardization, analysis and reporting. In addition, the probability of case detection for 20 diseases and welfare conditions was quantified using a scenario tree modelling approach, with input data based on literature and expert opinion. The sensitivity of MI appeared to be very high to detect most of the conditions studied because MI is performed at batch level and applied to a high number of birds per batch.

Anisotropy minimization via least squares method for transformation optics.

In this work the least squares method is used to reduce anisotropy in transformation optics technique. To apply the least squares method a power series is added on the coordinate transformation functions. The series coefficients were calculated to reduce the deviations in Cauchy-Riemann equations, which, when satisfied, result in both conformal transformations and isotropic media. We also present a mathematical treatment for the special case of transformation optics to design waveguides. To demonstrate the proposed technique a waveguide with a 30° of bend and with a 50% of increase in its output width was designed. The results show that our technique is simultaneously straightforward to be implement and effective in reducing the anisotropy of the transformation for an extremely low value close to zero.

Roots of the invasive species Carduus nutans L. and C. acanthoides L. produce large amounts of aplotaxene, a possible allelochemical.

The invasive thistle Carduus nutans has been reported to be allelopathic, yet no allelochemicals have been identified from the species. In a search for allelochemicals from C. nutans and the closely related invasive species C. acanthoides, bioassay-guided fractionation of roots and leaves of each species were conducted. Only dichloromethane extracts of the roots of both species contained a phytotoxin (aplotaxene, (Z,Z,Z)-heptadeca-1,8,11,14-tetraene) with sufficient total activity to potentially act as an allelochemical. Aplotaxene made up 0.44 % of the weight of greenhouse-grown C. acanthoides roots (ca. 20 mM in the plant) and was not found in leaves of either species. It inhibited growth of lettuce 50 % (I 50) in soil at a concentration of ca. 0.5 mg g(-1) of dry soil (ca. 6.5 mM in soil moisture). These values gave a total activity in soil value (molar concentration in the plant divided by the molarity required for 50 % growth inhibition in soil = 3.08) similar to those of some established allelochemicals. The aplotaxene I 50 for duckweed (Lemna paucicostata) in nutrient solution was less than 0.333 mM, and the compound caused cellular leakage of cucumber cotyledon discs in darkness and light at similar concentrations. Soil in which C. acanthoides had grown contained aplotaxene at a lower concentration than necessary for biological activity in our short-term soil bioassays, but these levels might have activity over longer periods of time and might be an underestimate of concentrations in undisturbed and/or rhizosphere soil.

Pharmacological activities of cilantro's aliphatic aldehydes against Leishmania donovani.

Leishmaniasis is a chronic infectious disease caused by different Leishmania species. Global occurrences of this disease are primarily limited to tropical and subtropical regions. Treatments are available; however, patients complain of side effects. Different species of plants have been screened as a potential source of new drugs against leishmaniasis. In this study, we investigated the antileishmanial activity of cilantro (Coriandrum sativum) essential oil and its main components: (E)-2-undecenal, (E)-2-decenal, (E)-2-dodecenal, decanal, dodecanal, and tetradecanal. The essential oil of C. sativum leaves inhibits growth of Leishmani donovani promastigotes in culture with an IC50 of 26.58 ± 6.11 µg/mL. The aliphatic aldehydes (E)-2-decenal (7.85 ± 0.28 µg/mL), (E)-2-undecenal (2.81 ± 0.21 µg/mL), and (E)-2-dodecenal (4.35 ± 0.15 µg/mL), all isolated from C. sativum essential oil, are effective inhibitors of in vitro cultures of L. donovani promastigotes. Aldehydes (E)-2-decenal, (E)-2-undecenal, and (E)-2-dodecenal were also evaluated against axenic amastigotes and IC50 values were determined to be 2.47 ± 0.25 µg/mL, 1.25 ± 0.11 µg/mL, and 4.78 ± 1.12 µg/mL, respectively. (E)-2-Undecenal and (E)-2-dodecenal demonstrated IC50 values of 5.65 ± 0.19 µg/mL and 9.60 ± 0.89 µg/mL, respectively, against macrophage amastigotes. These cilantro compounds showed no cytotoxicity against THP-1 macrophages.

Mevalonic Aciduria in a Pediatric Patient: A Case Report and Literature Review of Neuroimaging Findings.

Mevalonic aciduria is a rare autosomal recessive disorder resulting from mevalonate kinase deficiency. Neuroimaging findings associated with the disease have been documented in only a few case reports. We present a case of mevalonic aciduria with both already reported and novel neuroimaging findings and conduct a literature review regarding the role of neuroimaging in the understanding and diagnosis of mevalonate kinase deficiency disorders. The brain magnetic resonance imaging of the reported case revealed several notable findings, including polymicrogyric cortical thickening, an interhypothalamic adhesion or small hypothalamic hamartoma (findings not classically associated with mevalonic aciduria), and mild cerebellar atrophy. This case underscores the significance of recognizing the diverse spectrum of neuroimaging findings associated with the disease, encompassing both well-documented features and those that have not been traditionally reported.

A multinational survey of companion animal veterinary clinicians: How can antimicrobial stewardship guidelines be optimised for the target stakeholder?

Antimicrobial stewardship initiatives are widely regarded as a cornerstone for ameliorating the global health impact of antimicrobial resistance. Within companion animal health, such efforts have largely focused on development and dissemination of antimicrobial stewardship guidelines (ASGs). However, there have been few attempts to understand veterinarian attitudes towards and knowledge of ASGs or to determine how awareness regarding ASGs might best be increased. An online survey regarding ASGs was formulated for veterinarians who treat companion animals. The survey was distributed across 46 European and associated countries between 12 January and 30 June, 2022. In total, 2271 surveys were completed, with 64.9% of respondents (n = 1474) reporting awareness and usage of at least one ASG. Respondents from countries with greater awareness of ASGs tended to report more appropriate use of antimicrobials (Spearman's rank coefficient = 0.6084, P ≤ 0.001), with respondents from countries with country-specific ASGs tending to score highest across both awareness and appropriate use domains. Respondents prioritised guidance around antimicrobial choice (82.0%, n = 1863), duration of treatment (66.0%, n = 1499), and dosage (51.9%, n = 1179) for inclusion in future ASGs, with 78.0% (n = 1776) of respondents preferring ASGs to be integrated into their patient management system. Awareness of ASGs and their use in companion animal veterinary practice appears to be greater than previously reported, with respondents tending to report antimicrobial prescription decision making broadly in line with current clinical recommendations. However, further initiatives aimed at maximising accessibility to ASGs both within countries and individual veterinary practices are recommended.

The effect of total sleep deprivation on autonomic nervous system and cortisol responses to acute stressors in healthy individuals: A systematic review.

OBJECTIVE: To synthesise the literature examining the autonomic nervous system (ANS) and cortisol responses to an acute stressor following total sleep deprivation (TSD) in healthy adult subjects. METHODS: We conducted a systematic review (CRD42022293857) following the latest PRISMA statement. We searched Medline (via Ovid), Embase (via Ovid), PsycINFO (via Ovid), CINAHL complete and Scopus databases, without year restriction, using search terms related to "sleep deprivation", "stress", "autonomic nervous system" and "cortisol". Two independent team members used pre-defined inclusion/exclusion criteria to assess eligibility and extract data. We used RoB 2 to assess the risk of bias in randomised controlled trials, and ROBINS-I for non-randomised studies. RESULTS: Sixteen studies, with 581 participants (mean age = 29 ± 12 years), were eligible for inclusion in the descriptive syntheses. Half of the studies (n = 8) were conducted in the United States of America. The most commonly used study designs were randomised crossover studies (n = 7) and randomised controlled trials (n = 5). Most studies used a single night of TSD (n = 13) which was followed by a psychological (n = 6), physical (n = 5) or psychological and physical (n = 5) acute stressor event. Heart rate (n = 8), cortisol (n = 7) and blood pressure (n =6) were the most reported outcomes, while only a single study used forearm vascular conductance and forearm blood flow. Ten studies found that TSD changed, at least, one marker of ANS or cortisol response. TSD compared with a sleep control condition increased cortisol level (n=1), systolic blood pressure (n=3), diastolic blood pressure (n=2), mean arterial pressure (n=1), and electrodermal activity (n=1) after acute stress. Also, compared with a sleep control, TSD blunted cortisol (n=2), heart rate (n=1) and systolic blood pressure (n=2) responses after acute stress. However, TSD did not change ANS or cortisol responses to acute stressors in 73 % of the total reported outcomes. Furthermore, 10 RCT studies (62.5 %) were assigned as "some concerns" and two RCT studies (12.5 %) were attributed "high" risk of bias. Additionally, one non-randomised trial was classified as "moderate" and three non-randomised trials as "serious" risk of bias. CONCLUSION: The markers of ANS and cortisol responses to acute stress after TSD in healthy individuals reveal a scarcity of consistent evidence. The included studies present enough evidence that TSD induces either blunted or exaggerated ANS or cortisol responses to laboratory stresses supporting the "bidirectional multi-system reactivity hypothesis.". It appears that a comprehensive understanding of this phenomenon still lacks robust evidence, and further research is needed to clarify these relationships.

Enhanced Sampling in Molecular Dynamics Simulations: How Many MD Snapshots can be Needed to Reproduce the Biological Behavior?

Since its early days in the 19th century, medicinal chemistry has concentrated its efforts on the treatment of diseases, using tools from areas such as chemistry, pharmacology, and molecular biology. The understanding of biological mechanisms and signaling pathways is crucial information for the development of potential agents for the treatment of diseases mainly because they are such complex processes. Given the limitations that the experimental approach presents, computational chemistry is a valuable alternative for the study of these systems and their behavior. Thus, classical molecular dynamics, based on Newton's laws, is considered a technique of great accuracy, when appropriated force fields are used, and provides satisfactory contributions to the scientific community. However, as many configurations are generated in a large MD simulation, methods such as Statistical Inefficiency and Optimal Wavelet Signal Compression Algorithm are great tools that can reduce the number of subsequent QM calculations. Accordingly, this review aims to briefly discuss the importance and relevance of medicinal chemistry allied to computational chemistry as well as to present a case study where, through a molecular dynamics simulation of AMPK protein (50 ns) and explicit solvent (TIP3P model), a minimum number of snapshots necessary to describe the oscillation profile of the protein behavior was proposed. For this purpose, the RMSD calculation, together with the sophisticated OWSCA method was used to propose the minimum number of snapshots.

Laryngotracheomalacia in a Patient with Mosaic Trisomy 8.

Mosaic trisomy 8 is a condition characterized by a great phenotypic and cytogenetic variability whose incidence ranges around 1 in 25,000 to 50,000 live births. Here, we report a mosaic trisomy 8 patient presenting laryngotracheomalacia, an uncommon finding, analyzing its possible role over morbidity, and mortality. The patient was a boy who, after birth, had tachypnea and paleness. He presented periods of respiratory dysfunction with need of ventilatory support. Respiratory syncytial virus test was positive. Naso fibrobronchoscopy showed moderate laryngotracheomalacia. He also had recurrent episodes of pneumonia and difficulty in withdrawing continuous positive airway pressure. The patient also presented leucoma, abnormal and low-set ears, pectus excavatum, clenched fists with overlapping fingers, cryptorchidism, clubfeet, and deep longitudinal plantar creases. G-bands by Trypsin using giemsa (GTG-banding) karyotype from a peripheral blood sample revealed a mosaic trisomy 8: mos 47,XY, + 8[15]/46,XY[7]. At 4 months, the patient developed respiratory failure, and a chest computed tomography scan showed areas of atelectasis and gross fibroatelectatic striae. He ended up presenting clinical worsening and died at 4 months and 8 days. In our literature review, we found some reports describing patients with mosaic trisomy 8 and laryngotracheomalacia. However, we cannot rule out the possibility that this association could be casual, since laryngotracheomalacia is a relatively common finding in children. Therefore, more studies are still necessary to understand the possible relation between both conditions and the role of laryngotracheomalacia over morbidity and prognosis of mosaic trisomy 8 patients.

Timed-artificial insemination protocols for Bos indicus beef heifers: Evaluation of protocol length and variations in prostaglandin F2α treatments.

The aim was to compare reproductive outcomes of Nelore heifers submitted to timed AI (TAI) protocols, with 7 or 9 d of permanence of the intravaginal progesterone (P4) device and different times of prostaglandin F2α (PGF) administration, for first (n = 935) and second (n = 530) services. On Day -24, heifers without corpus luteum (CL) underwent a protocol for induction of ovulation. On Day 0, heifers received a P4 device (0.5 g) and 1.5 mg estradiol (E2) benzoate. In order for the TAI to be carried out on the same day, these treatments were performed 2 d later on the heifers treated with the 7-d protocol. Additionally, heifers received 0.5 mg PGF at different times, resulting in four experimental groups: 9dP4-PGFd9 (n = 365); 9dP4-PGFd7 (n = 369); 9dP4-PGFd0&9 (n = 364); 7dP4-PGFd0&7 (n = 367). These nomenclatures indicate for how many d the P4 device was kept and the specific day on which PGF was given. At P4 removal, all heifers received 0.5 mg E2 cypionate and 200 IU eCG, and TAI was performed 2 d later. Effects were considered significant when P ≤ 0.05 (superscript letters a,b) whereas a tendency was assumed when 0.05 < P ≤ 0.10. Groups 9dP4-PGFd0&9 and 7dP4-PGFd0&7 had lower percentage of heifers with CL at P4 removal. The diameter (mm) of the dominant follicle (DF) was affected by treatment at P4 removal (9dP4-PGFd9: 11.3 ± 0.3b; 9dP4-PGFd7: 11.8 ± 0.2ab; 9dP4-PGFd0&9: 12.6 ± 0.2a; 7dP4-PGFd0&7: 10.8 ± 0.2c) and at TAI (9dP4-PGFd9: 12.7 ± 0.3ab; 9dP4-PGFd7: 13.2 ± 0.2a; 9dP4-PGFd0&9: 13.4 ± 0.2a; 7dP4-PGFd0&7: 12.4 ± 0.3b). Expression of estrus (%) was affected by treatment (9dP4-PGFd9: 89.6a; 9dP4-PGFd7: 93.5a; 9dP4-PGFd0&9: 88.2ab; 7dP4-PGFd0&7: 85.6b). There were no differences among treatments for P/AI on Day 40 (30-35 d post AI), final P/AI (between Day 70 and parturition) and pregnancy loss (between Day 40 and final P/AI). When the permanence of the P4 device was compared, regardless of PGF treatments, 9-d protocols resulted in greater DF diameter at P4 removal and at TAI, and greater expression of estrus (90.4 vs. 85.6%) than the 7-d protocol. Despite that, the 7-d protocol resulted in greater P/AI on Day 40 (55.3 vs. 49.1%). In addition, there was an interaction between protocol duration and body weight, in which heavier heifers (≥ 307 kg) had greater P/AI when treated with the 7-d protocol, in comparison to 9-d. In conclusion, longer TAI protocols (9 d of P4 device duration) resulted in greater DF diameter and expression of estrus. However, the shorter TAI protocol (7 d of P4 device duration) produced greater P/AI on Day 40, particularly in heavier heifers. Within 9-d protocols, the additional dose of PGF on Day 0 or the anticipation of the PGF to Day 7 did not influence fertility.

Advancing healthcare with artificial intelligence: diagnostic accuracy of machine learning algorithm in diagnosis of diabetic retinopathy in the Brazilian population.

BACKGROUND: In healthcare systems in general, access to diabetic retinopathy (DR) screening is limited. Artificial intelligence has the potential to increase care delivery. Therefore, we trained and evaluated the diagnostic accuracy of a machine learning algorithm for automated detection of DR. METHODS: We included color fundus photographs from individuals from 4 databases (primary and specialized care settings), excluding uninterpretable images. The datasets consist of images from Brazilian patients, which differs from previous work. This modification allows for a more tailored application of the model to Brazilian patients, ensuring that the nuances and characteristics of this specific population are adequately captured. The sample was fractionated in training (70%) and testing (30%) samples. A convolutional neural network was trained for image classification. The reference test was the combined decision from three ophthalmologists. The sensitivity, specificity, and area under the ROC curve of the algorithm for detecting referable DR (moderate non-proliferative DR; severe non-proliferative DR; proliferative DR and/or clinically significant macular edema) were estimated. RESULTS: A total of 15,816 images (4590 patients) were included. The overall prevalence of any degree of DR was 26.5%. Compared with human evaluators (manual method of diagnosing DR performed by an ophthalmologist), the deep learning algorithm achieved an area under the ROC curve of 0.98 (95% CI 0.97-0.98), with a specificity of 94.6% (95% CI 93.8-95.3) and a sensitivity of 93.5% (95% CI 92.2-94.9) at the point of greatest efficiency to detect referable DR. CONCLUSIONS: A large database showed that this deep learning algorithm was accurate in detecting referable DR. This finding aids to universal healthcare systems like Brazil, optimizing screening processes and can serve as a tool for improving DR screening, making it more agile and expanding care access.

CORE-VTRCC Cruise Report: Geophysical Acquisition and Seafloor Sampling along the Vitória-Trindade Ridge.

This work reports the data obtained by the multidisciplinary cruise CORE-VTRCC surveying on the region around the Vitória-Trindade Ridge (VTR) aboard the vessel NHo Cruzeiro do Sul (October 18th to November 6th, 2021). The main objectives of the VTRCC Cruise were (1) to assess the role of the VTR as an oceanographic barrier for bottom currents along the Brazilian margin; and (2) to characterize the morphology of the volcanic seamounts and its relationships with the carbonate sediments that cover it. For that, we performed multibeam bathymetry, magnetometry, high-resolution multichannel seismic survey, subbottom profiling survey, and seafloor sampling along the VTR and along the Columbia Deepwater Channel. The raw dataset was processed for quality control and organized for public access. When required, additional geophysical processing occurred to improve data quality. Seafloor samples are characterized based on the concentration of its biofacies, the sediment grain-sizes and the morphology of rhodoliths sampled. The dataset reveals comprehensively the geological and oceanographic heterogeneity of the region around the VTR.

Free breathing three-dimensional gradient echo-sequence with radial data sampling (radial 3D-GRE) examination of the pancreas: Comparison with standard 3D-GRE volumetric interpolated breathhold examination (VIBE).

PURPOSE: To evaluate the diagnostic performance of free breathing three-dimensional gradient echo-sequence with radial data sampling (radial 3D-GRE) in MR imaging of the normal and diseased pancreas, using standard 3D-GRE for comparison in cooperative patients, and to perform a preliminary assessment in noncooperative patients. MATERIALS AND METHODS: One hundred and eight consecutive patients underwent 1.5 Tesla MR imaging of the abdomen that included pre- and postcontrast free breathing radial 3D-GRE. The sequences were evaluated by two radiologists retrospectively, independently, and blindly. The results were compared using Wilcoxon-Mann-Whitney test. Kappa statistics were used to measure the extent of agreement between the reviewers. RESULTS: The average scores indicated that the overall images quality of radial 3D-GRE was lower than 3D-GRE-VIBE in both pre- and postcontrast study (P = 0.0172 and 0.0001), however it achieved a rating that approximated good. In all patients, radial 3D-GRE had a mild extent of streak artifact, pulsation, susceptibility, and respiratory artifact. Radial 3D-GRE approximated good results for pancreatic edge sharpness and pancreatic ductal clarity, and did not differ significantly between cooperative and noncooperative patients. Respiratory artifact was worse in cooperative than in noncooperative patients (P = 0.02). Demonstration of pancreatic disease was slightly inferior with radial 3D-VIBE, but quality approximated good. CONCLUSION: Free breathing radial 3D-GRE may be applicable for pancreatic MR imaging in patients who are unable to suspend respiration.

Antimicrobial usage in farm animal practices in the UK: A mixed-methods approach.

Antimicrobial resistance (AMR) is a growing One Health problem. Monitoring antimicrobial usage in farm animals is crucial for tackling AMR. A cohort study using the electronic clinical records during 2019 from 23 farm animal veterinary practices across the UK belonging to two corporate groups, with a range of 2-14 veterinarians per practice, estimated the usage of antimicrobials and highest priority critically important antimicrobials (HP-CIAs). Risk factors for using HP-CIAs were evaluated using hierarchical mixed-effects logistic regression modelling with practice ID and farm ID added as random effects. Using a qualitative approach, veterinarians from one of the participating practice groups were recruited for a qualitative study to explore the barriers and facilitators in relation to antimicrobial use. Semi-structured interviews were conducted with participants and analysed thematically. During the year 2019, 98,824 antimicrobial prescribing events overall were recorded from the treatment records of the 23 participating practices. The median count of antimicrobial events per practice was 3226 (range 263-22,159). There were 17,111/98,824 (17.3%) HP-CIAs events overall, with a median of 15.4% at practice level (range 4.8-22.1%). Penicillins were the most frequently used antimicrobials 29,539/98,824 (29.9%) followed by tetracyclines 19,015/98,824 (19.2%). HP-CIA use was strongly clustered, with more clustering seen at the farm level (intraclass correlation coefficient (ICC)= 0.56) than at the practice level (ICC= 0.32). Country, route of administration, season and practice type were significantly associated with the usage of HP-CIAs. Four main themes were identified from the analysis of the veterinarians' interviews: pressure from the industry, drug-related factors, knowledge level of veterinarians and clinical factors. Supermarket contracts and farm assurance schemes were facilitators for reducing antimicrobial use and the use of HP-CIAs. Ease of administration and the withdrawal period of the antimicrobials influenced veterinarians' choice of antimicrobials. The clinical condition and clinical signs presented on farm were reported to influence participating veterinarians' prescribing decision. Participants showed a good understanding of AMR, responsible use of antimicrobials and the term 'critically important antimicrobials'. In conclusion, integrating the quantitative and qualitative findings can inform policymaking on antimicrobials stewardship in farm practice. By estimating the relative levels of clustering of antimicrobial use at the practice and farm level, as well as identifying major risk factors for using HP-CIAs, more targeted interventions can be designed to promote responsible antimicrobial use in farm practice. Furthermore, better understanding the industry pressures on farms to reduce antimicrobials usage could reduce the barriers for responsible antimicrobial use by veterinarians.