Ensuring progress on sustainable access to effective antibiotics at the 2024 UN General Assembly: a target-based approach.

Rising antimicrobial resistance (AMR) is a global health crisis for countries of all economic levels, alongside the broader challenge of access to antibiotics. As a result, development goals for child survival, healthy ageing, poverty reduction, and food security are at risk. Preserving antimicrobial effectiveness, a global public good, requires political will, targets, accountability frameworks, and funding. The upcoming second high-level meeting on AMR at the UN General Assembly (UNGA) in September, 2024, is evidence of political interest in addressing the problem of AMR, but action on targets, accountability, and funding, absent from the 2016 UNGA resolution, is needed. We propose ambitious yet achievable global targets for 2030 (relative to a prepandemic 2019 baseline): a 10% reduction in mortality from AMR; a 20% reduction in inappropriate human antibiotic use; and a 30% reduction in inappropriate animal antibiotic use. Given national variation in current levels of antibiotic use, these goals (termed the 10-20-30 by 2030) should be met within a framework of universal access to effective antibiotics. The WHO Access, Watch, Reserve (AWARE) system can be used to define, monitor, and evaluate appropriate levels of antibiotic use and access. Some countries should increase access to narrow-spectrum, safe, and affordable (Access) antibiotics, whereas others should discourage the inappropriate use of broader-spectrum (Watch) and last-resort (Reserve) antibiotics; AWARE targets should use a risk-based, burden-adjusted approach. Improved infection prevention and control, access to clean water and sanitation, and vaccination coverage can offset the selection effects of increased antibiotic use in low-income settings. To ensure accountability and global scientific guidance and consensus, we call for the establishment of the Independent Panel on Antimicrobial Access and Resistance and the support of leaders from low-income and middle-income countries.

Highly pathogenic avian influenza: Unprecedented outbreaks in Canadian wildlife and domestic poultry.

Canada experienced a wave of HPAI H5N1 outbreaks in the spring of 2022 with millions of wild and farmed birds being infected. Seabird mortalities in Canada have been particularly severe on the Atlantic Coast over the summer of 2022. Over 7 million birds have been culled in Canada, and outbreaks continue to profoundly affect commercial bird farms across the world. This new H5N1 virus can and has infected multiple mammalian species, including skunks, foxes, bears, mink, seals, porpoises, sea lions, and dolphins. Viruses with mammalian adaptations such as the mutations PB2-E627K, E627V, and D701N were found in the brain of various carnivores in Europe and Canada. To date this specific clade of H5N1 virus has been identified in less than 10 humans. At the ground level, awareness should be raised among frontline practitioners most likely to encounter patients with HPAI.

Le Canada a vécu un vague d'éclosions de grippe aviaire de souche H5N1 hautement pathogène au printemps 2022 lorsque des millions d'oiseaux sauvages et d'oiseaux d'élevage ont été infectés. La mortalité des oiseaux marins au Canada a été particulièrement marquée sur la côte Atlantique pendant l'été 2022. Plus de sept millions d'oiseaux ont été abattus au Canada, et les éclosions continuent de nuire profondément aux élevages commerciaux d'oiseaux dans le monde. Ce nouveau virus H5N1 peut infecter de multiples espèces de mammifères, y compris des mouffettes, des renards, des ours, des visons, des phoques, des marsouins, des otaries et des dauphins. Les virus adaptés aux mammifères et porteurs des mutations PB2-E627K, E627V et D701N, ont été observés dans le cerveau de divers carnivores de l'Europe et du Canada. Jusqu'à présent, ce clade du virus H5N1 a été dépisté chez moins de dix humains. Sur le terrain, il est important de sensibiliser les praticiens de première ligne qui sont plus susceptibles de voir des patients atteints de la grippe aviaire de souche hautement pathogène.

Effects of virgin and BaP-adsorbed microplastics ingestion by Manila clams (Ruditapes philippinarum).

Numerous microplastic-related studies have investigated the impact of plastic materials on the marine food chain. In this study, Manila clams were exposed to microplastic (MP) of various polymer types, shapes, and concentrations to determine the ingestion selectivity and adverse effects caused. Benzo[a]pyrene was introduced as the second stressor to investigate the role of MP as a vector of contaminant. The result of a 2-day acute exposure showed that clams are more likely to ingest those in sphere shapes due to their similarity to microalgae. The feeding rate continuously declined when clams were exposed to at least 2to/L particles. Additionally, co-exposure of MP and B[a]P resulted in higher DNA fragmentation but lower catalase activity compared to single exposure to MP. Our study revealed that the uptake of MP by clams is not only determined by its shape and concentration but also by the presence of existing contaminants.

Cost-effective, portable, patient-dedicated three-dimensional automated breast ultrasound for point-of-care breast cancer screening.

Breast cancer screening has substantially reduced mortality across screening populations. However, a clinical need persists for more accessible, cost-effective, and robust approaches for increased-risk and diverse patient populations, especially those with dense breasts where screening mammography is suboptimal. We developed and validated a cost-effective, portable, patient-dedicated three-dimensional (3D) automated breast ultrasound (ABUS) system for point-of-care breast cancer screening. The 3D ABUS system contains a wearable, rapid-prototype 3D-printed dam assembly, a compression assembly, and a computer-driven 3DUS scanner, adaptable to any commercially available US machine and transducer. Acquisition is operator-agnostic, involves a 40-second scan time, and provides multiplanar 3D visualization for whole-breast assessment. Geometric reconstruction accuracy was evaluated with a 3D grid phantom and tissue-mimicking breast phantoms, demonstrating linear measurement and volumetric reconstruction errors < 0.2 mm and < 3%, respectively. The system's capability was demonstrated in a healthy male volunteer and two healthy female volunteers, representing diverse patient geometries and breast sizes. The system enables comfortable ultrasonic coupling and tissue stabilization, with adjustable compression to improve image quality while alleviating discomfort. Moreover, the system effectively mitigates breathing and motion, since its assembly affixes directly onto the patient. While future studies are still required to evaluate the impact on current clinical practices and workflow, the 3D ABUS system shows potential for adoption as an alternative, cost-effective, dedicated point-of-care breast cancer screening approach for increased-risk populations and limited-resource settings.

Virtual Visits for Developmental Screening in High-Risk Infants.

INTRODUCTION: The High-Risk Infant Follow-Up program screens neonatal intensive care unit graduates for developmental delays and refers patients to physical, occupational, or speech therapy. At Kaiser Permanente Downey, the High-Risk Infant Follow-Up program assessed development via video visits during the COVID-19 pandemic. This study compares rates of enrollment in and referral to therapies and California Regional Center services between infants assessed by video visits and those assessed in person. METHODS: Study participants included infants in the High-Risk Infant Follow-Up program between March 2020 and March 2021 with developmental assessments at adjusted ages 6, 12, and 18 months. Rates of enrollment in services and referral to physical, occupational, and speech therapy and Regional Center services were compared between infants assessed virtually and in person. RESULTS: There were no significant differences in rates of enrollment or referral to physical, occupational, or speech therapy services or Regional Center services. The rate of referral at any of the 3 visits was 8.6% at in-person visits and 10.9% at virtual visits (p = 0.49). Infants whose first visit was virtual were just as likely to complete all 3 developmental assessments as those whose first visit was in person. DISCUSSION: The COVID-19 pandemic stay-at-home orders provided a "natural experiment" demonstrating the effectiveness of virtual visits as compared to in-person visits. Although the developmental assessment tool used was not standardized to be used virtually, virtual visits were just as likely to result in referrals to services and did not lead to loss of follow-up. CONCLUSION: Virtual visits may be useful and convenient for some families, but further study is required.

The effects of ambient temperature exposure on feline fecal metabolome.

Introduction: The fecal metabolome provides insight into overall gastrointestinal and microbial health. Methods for fecal sample storage in metabolomics research vary, however, making comparisons within current literature difficult. This study investigated the effect of ambient temperature exposure on microbial-derived metabolites of feline fecal samples. Methods: Fecal samples were collected from 11 healthy cats from a local boarding facility. Samples were manually homogenized and aliquoted. The first aliquot was frozen at -80°C within 1 hour of defecation, and remaining samples were exposed to ambient temperature for 2, 4, 6, 8, 12, and 24 h prior to freezing at -80°C. Fecal metabolites were quantified using 1H NMR spectroscopy. Fifty metabolites were grouped into six categories (27 amino acids, 8 fatty acids, 5 sugars, 3 alcohols, 2 nitrogenous bases, 5 miscellaneous). Results: Concentrations of 20 out of 50 metabolites significantly differed due to ambient temperature exposure (7 amino acids, 6 fatty acids, 2 alcohols, 1 nitrogenous base, 4 miscellaneous). The earliest detected changes occurred 6 h post-defecation for cadaverine and fumaric acid. Discussion: This study shows ambient temperature exposure alters the composition of the feline fecal metabolome, but short-term (up to 4 h) exposure prior to storage in the freezer seems to be acceptable.

Effect of dietary iron supplementation on the equine fecal microbiome.

Iron is an essential element for all living organisms, including bacteria, as several virulence factors and replication components are influenced by iron concentration. The objective of this study was to determine whether the composition and diversity of the fecal microbiota of adult horses are affected by supplemental dietary iron. Ten clinically healthy horses were randomly divided into a control and an iron-supplemented group (n = 5). The treated group was supplemented with oral ferrous sulphate monohydrate (720 ppm of iron), whereas the control group received 320 ppm of iron daily for 15 d. Fecal samples were collected before and 5, 10, 15, and 30 d after supplementation and frozen at -80°C. DNA was sequenced using an Illumina MiSeq platform and data were analyzed using the software Mothur and linear discriminant analysis (LDA) effect size (LEfSe). Iron supplementation caused no change in the overall composition of the fecal microbiota, but some minor changes were observed in the low-abundant bacteria, as well as an increased alpha diversity after 15 d of supplementation. Significant differences in community composition of the fecal microbiota over time were observed in both groups, highlighting the importance of a control group, as there are variables that cannot be controlled in microbiome studies.

Le fer est un élément essentiel pour tous les organismes vivants, y compris les bactéries, car plusieurs facteurs de virulence et composants de réplication sont influencés par la concentration en fer. L'objectif de cette étude était de déterminer si la composition et la diversité du microbiote fécal des chevaux adultes sont affectées par la supplémentation en fer alimentaire. Dix chevaux cliniquement sains ont été divisés au hasard en un groupe témoin et un groupe supplémenté en fer, n = 5 par groupe. Le groupe traité a reçu un supplément oral de sulfate ferreux monohydraté (720 ppm de fer) et le groupe témoin a reçu 320 ppm de fer par jour pendant 15 jours. Des échantillons fécaux ont été prélevés avant la supplémentation et 5, 10, 15 et 30 jours après la supplémentation puis congelés à −80 °C. L'ADN a été séquencé à l'aide de la plateforme Illumina MiSeq et les données ont été analysées à l'aide des logiciels Mothur et analyse de la fonction discriminante linéaire taille de l'effet LefSe. La supplémentation en fer n'a provoqué aucun changement dans la composition du microbiote fécal, mais certains changements ont été observés chez les bactéries peu abondantes, ainsi qu'une augmentation de la diversité alpha après 15 jours de supplémentation. Au fil du temps, des différences significatives dans la composition de la communauté bactérienne ont été observées dans les deux groupes, soulignant l'importance d'un groupe témoin, car il existe des variables qui ne peuvent être contrôlées dans les études sur le microbiome.(Traduit par les auteurs).

Putting prospection into practice: Methodological considerations in the use of episodic future thinking to reduce delay discounting and maladaptive health behaviors.

In recent years, episodic future thinking (EFT) has emerged as a promising behavioral intervention to reduce delay discounting or maladaptive health behaviors; however, considerable methodological heterogeneity in methods for eliciting engagement in EFT has been observed in prior research. In this narrative review, we briefly describe methods for generating EFT cues, the content of EFT cues, common control conditions for experiments utilizing EFT, and considerations for cue delivery and implementation. Where possible, we make suggestions for current best practices in each category while identifying gaps in knowledge and potential areas of future research. Finally, we conclude by using the NIH Stage model to better frame the current state of the literature on EFT and propose gaps to be addressed if EFT is to be both an efficacious and effective behavioral intervention.

Spatial patterns of Borrelia burgdorferi, Borrelia miyamotoi and Anaplasma phagocytophilum detected in Ixodes spp. ticks from Canadian companion animals, 2019-2020.

Increasing temperatures due to climate change have contributed to a northward range expansion of Ixodes scapularis ticks in Canada. These ticks harbour pathogens of public and animal health significance, including Borrelia burgdorferi and Anaplasma phagocytophilum, which cause Lyme disease and anaplasmosis, respectively, in humans, dogs and horses, and Borrelia miyamotoi, which causes a flu-like relapsing fever in humans. To address the risks associated with these vector-borne zoonotic diseases, continuous tick surveillance is advised. This study examined spatial patterns of B. burgdorferi, B. miyamotoi and A. phagocytophilum from ticks submitted through a national study on ticks of companion animals. From 1 April 2019 to 31 March 2020, we received a total of 1541 eligible submissions from 94 veterinary clinics across Canada. Individual and pooled samples of a maximum of either 5 I. scapularis, I. pacificus or I. angustus samples from the same animal and of the same life stage were screened using real-time PCR targeting genes 23S rRNA for Borrelia spp. and msp2 for A. phagocytophilum. Confirmatory testing was conducted on all 23S rRNA positive samples using a duplex assay for ospA and flaB to differentiate B. burgdorferi and B. miyamotoi, respectively. Prevalence estimates were highest (>20%) for B. burgdorferi in southwestern Manitoba, eastern Ontario, southwestern Quebec, New Brunswick and Nova Scotia. Estimates of B. miyamotoi and A. phagocytophilum were much lower (<5%), except for higher A. phagocytophilum (>5%) estimates for southern Manitoba, eastern Ontario and Prince Edward Island. Findings from this study, combined with other surveillance approaches, can be used to guide veterinary and public health approaches for ticks and tick-borne diseases.

Effect of Galcanezumab on Total Pain Burden in Patients Who Had Previously Not Benefited from Migraine Preventive Medication (CONQUER Trial): A Post Hoc Analysis.

INTRODUCTION: In evaluating therapies for migraine prevention, emphasis is placed on frequency and less attention is paid to duration or severity. Total pain burden (TPB) combines frequency, duration, and severity of migraine headache, and has the potential to further characterize the benefit of preventive treatment using a single composite measure. TPB was previously used to characterize response to galcanezumab (GMB) in patients with migraine. In this post hoc analysis we assessed the impact of GMB in lowering TPB in patients who had previously not benefited from two to four categories of migraine preventive medication. METHODS: CONQUER trial patients (N = 462), 18-75 years old who had previously not benefited from two to four categories of migraine preventive medication, were randomized (1:1) to monthly placebo or GMB 120 mg with 240 mg loading dose. For each patient, monthly TPB in severity-weighted hours was calculated by multiplying migraine headache duration (hours) by maximum severity for each migraine headache day, then summing these daily scores over the month for the monthly score. Changes from baseline in monthly TPB across months 1-3 were analyzed. Spearman correlations between TPB and scores on the Migraine-Specific Quality-of-Life Questionnaire (MSQ) total and Migraine Disability Assessment Scale (MIDAS) were assessed at baseline. RESULTS: Mean (SD) baseline monthly TPB was 192.1 (158.3) and 188.2 (197.4) severity-weighted hours for GMB-treated and placebo-treated patients, respectively. Across the 3-month double-blind period, GMB-treated patients experienced significantly greater mean reductions from baseline in monthly TPB compared with placebo-treated patients, both for mean change (GMB - 82.7, placebo - 15.8, p < 0.001) and percentage change (GMB - 38.6%, placebo 9.4%, p < 0.001). Furthermore, baseline TPB correlated with MSQ score (r = - 0.39) and MIDAS score (r = 0.40), suggesting good association of TPB with functional and disability outcomes. CONCLUSION: GMB reduced mean TPB in patients who had previously not benefited from two to four categories of migraine preventive medication. TRIAL REGISTRATION: NCT03559257.

Spatially tracked whole-breast three-dimensional ultrasound system toward point-of-care breast cancer screening in high-risk women with dense breasts.

BACKGROUND: Mammographic screening has reduced mortality in women through the early detection of breast cancer. However, the sensitivity for breast cancer detection is significantly reduced in women with dense breasts, in addition to being an independent risk factor. Ultrasound (US) has been proven effective in detecting small, early-stage, and invasive cancers in women with dense breasts. PURPOSE: To develop an alternative, versatile, and cost-effective spatially tracked three-dimensional (3D) US system for whole-breast imaging. This paper describes the design, development, and validation of the spatially tracked 3DUS system, including its components for spatial tracking, multi-image registration and fusion, feasibility for whole-breast 3DUS imaging and multi-planar visualization in tissue-mimicking phantoms, and a proof-of-concept healthy volunteer study. METHODS: The spatially tracked 3DUS system contains (a) a six-axis manipulator and counterbalanced stabilizer, (b) an in-house quick-release 3DUS scanner, adaptable to any commercially available US system, and removable, allowing for handheld 3DUS acquisition and two-dimensional US imaging, and (c) custom software for 3D tracking, 3DUS reconstruction, visualization, and spatial-based multi-image registration and fusion of 3DUS images for whole-breast imaging. Spatial tracking of the 3D position and orientation of the system and its joints (J1-6 ) were evaluated in a clinically accessible workspace for bedside point-of-care (POC) imaging. Multi-image registration and fusion of acquired 3DUS images were assessed with a quadrants-based protocol in tissue-mimicking phantoms and the target registration error (TRE) was quantified. Whole-breast 3DUS imaging and multi-planar visualization were evaluated with a tissue-mimicking breast phantom. Feasibility for spatially tracked whole-breast 3DUS imaging was assessed in a proof-of-concept healthy male and female volunteer study. RESULTS: Mean tracking errors were 0.87 ± 0.52, 0.70 ± 0.46, 0.53 ± 0.48, 0.34 ± 0.32, 0.43 ± 0.28, and 0.78 ± 0.54 mm for joints J1-6 , respectively. Lookup table (LUT) corrections minimized the error in joints J1 , J2 , and J5 . Compound motions exercising all joints simultaneously resulted in a mean tracking error of 1.08 ± 0.88 mm (N = 20) within the overall workspace for bedside 3DUS imaging. Multi-image registration and fusion of two acquired 3DUS images resulted in a mean TRE of 1.28 ± 0.10 mm. Whole-breast 3DUS imaging and multi-planar visualization in axial, sagittal, and coronal views were demonstrated with the tissue-mimicking breast phantom. The feasibility of the whole-breast 3DUS approach was demonstrated in healthy male and female volunteers. In the male volunteer, the high-resolution whole-breast 3DUS acquisition protocol was optimized without the added complexities of curvature and tissue deformations. With small post-acquisition corrections for motion, whole-breast 3DUS imaging was performed on the healthy female volunteer showing relevant anatomical structures and details. CONCLUSIONS: Our spatially tracked 3DUS system shows potential utility as an alternative, accurate, and feasible whole-breast approach with the capability for bedside POC imaging. Future work is focused on reducing misregistration errors due to motion and tissue deformations, to develop a robust spatially tracked whole-breast 3DUS acquisition protocol, then exploring its clinical utility for screening high-risk women with dense breasts.

Fixation vs Arthroplasty for Femoral Neck Fracture in Patients Aged 40-59 Years: A Propensity-Score-Matched Analysis.

Background: Internal fixation (IF) has historically been favored for the treatment of femoral neck fractures (FNFs) in young, nongeriatric patients. However, recent literature reporting high reoperation rates among those receiving IF, taken in conjunction with favorable survivorship of modern bearing surfaces in total hip arthroplasty (THA), has begun to question this paradigm. Our study sought to compare outcomes between IF and THA for FNFs in patients aged 40-59 years. Methods: Using the Truven MarketScan Database, we performed a retrospective propensity-score-matched cohort study on patients aged 40-59 years who underwent surgical management of an isolated FNF (THA or IF). Patients with pathologic fracture were not included. Analysis was conducted on patients aged 40-49 and 50-59 years separately. A subgroup analysis was performed on those patients with 1 year and 3 years of follow-up. Multivariate analysis, controlling for baseline patient information, was then performed. Results: Seven hundred sevety-eight 40- to 49-year-old patients and 3470 50- to 59-year-old matched patients (IF and THA) were included in this study. A multivariate analysis found that patients aged 40-49 years who underwent IF were at higher odds of both 1-year (odds ratio 2.35, 95% confidence interval 1.22-4.54, P = .011) and 3-year (odds ratio 5.68, 95% confidence interval 2.21-14.60, P < .001) reoperation. Similar results were found in those aged 50-59 years. While complication rates were similar, postoperative anemia and 90-day visits to the emergency room were more common after THA in both age cohorts. Conclusions: While THA is associated with increased postoperative anemia and resource utilization compared with IF, patients aged 40-59 years who undergo IF for FNF are at increased risk of reoperation in the first 3 postoperative years. This information should be used to assist in shared decision-making with patients in this age group.

CIndex: compressed indexes for fast retrieval of FASTQ files.

MOTIVATION: Ultrahigh-throughput next-generation sequencing instruments continue to generate vast amounts of genomic data. These data are generally stored in FASTQ format. Two important simultaneous goals are space-efficient compressed storage of the genomic data and fast query performance. Toward that end, we introduce compressed indexing to store and retrieve FASTQ files. RESULTS: We propose a compressed index for FASTQ files called CIndex. CIndex uses the Burrows-Wheeler transform and the wavelet tree, combined with hybrid encoding, succinct data structures and tables REF and Rγ, to achieve minimal space usage and fast retrieval on the compressed FASTQ files. Experiments conducted over real publicly available datasets from various sequencing instruments demonstrate that our proposed index substantially outperforms existing state-of-the-art solutions. For count, locate and extract queries on reads, our method uses 2.7-41.66% points less space and provides a speedup of 70-167.16 times, 1.44-35.57 times and 1.3-55.4 times. For extracting records in FASTQ files, our method uses 2.86-14.88% points less space and provides a speedup of 3.13-20.1 times. CIndex has an additional advantage in that it can be readily adapted to work as a general-purpose text index; experiments show that it performs very well in practice. AVAILABILITY AND IMPLEMENTATION: The software is available on Github: https://github.com/Hongweihuo-Lab/CIndex. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Evaluation of antimicrobial prescriptions in dogs with suspected bacterial urinary tract disease.

BACKGROUND: Antimicrobials are commonly used to treat urinary tract disease in dogs. Understanding antimicrobial use is a critical component of antimicrobial stewardship efforts. HYPOTHESIS/OBJECTIVES: To evaluate antimicrobial prescriptions for dogs diagnosed with acute cystitis, recurrent cystitis, and pyelonephritis. ANIMALS: Dogs prescribed antimicrobials for urinary tract disease at veterinary practices in the United States and Canada. MATERIALS AND METHODS: A retrospective review of antimicrobial prescriptions was performed. RESULTS: The main clinical concerns were sporadic bacterial cystitis (n = 6582), recurrent cystitis (n = 428), and pyelonephritis (n = 326). Amoxicillin/clavulanic acid (2702, 41%), cefpodoxime (1024, 16%), and amoxicillin (874, 13%) were most commonly prescribed for sporadic bacterial cystitis. The median prescribed duration was 12 days (range, 3-60 days; interquartile range [IQR], 4 days). Shorter durations were used in 2018 (median, 10 days; IQR, 4 days) compared to both 2016 and 2017 (both median, 14 days; IQR, 4 days; P ≤ .0002). Amoxicillin/clavulanic acid (146, 33%), marbofloxacin (95, 21%), and cefpodoxime (65, 14%) were most commonly used for recurrent cystitis; median duration of 14 days (range, 3-77 days; IQR, 10.5 days). Amoxicillin/clavulanic acid (86, 26%), marbofloxacin (56, 17%), and enrofloxacin (36, 11%) were most commonly prescribed for pyelonephritis; however, 93 (29%) dogs received drug combinations. The median duration of treatment was 14 days (range, 3-77 days; IQR, 11 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Decreases in duration and increased use of recommended first-line antimicrobials were encouraging. Common drug choices and durations should still be targets for antimicrobial stewardship programs that aim to optimize antimicrobial use, concurrently maximizing patient benefits while minimizing antimicrobial use and use of higher tier antimicrobials.

Design and validation of an MRI-compatible mechatronic system for needle delivery to localized prostate cancer.

PURPOSE: Prostate cancer is the most common non-cutaneous cancer among men in the United States and is the second leading cause of cancer death in American men. (Siegel et al. [2019] CA: A Cancer J Clin.69(1):7-34.) Focal laser ablation (FLA) has the potential to control small tumors while preserving urinary and erectile function by leaving the neurovascular bundles and urethral sphincters intact. Accurate needle guidance is critical to the success of FLA. Multiparametric magnetic resonance images (mpMRI) can be used to identify targets, guide needles, and assess treatment outcomes. The purpose of this work was to design and evaluate the accuracy of an MR-compatible mechatronic system for in-bore transperineal guidance of FLA ablation needles to localized lesions in the prostate. METHODS: The mechatronic system was constructed entirely of non-ferromagnetic materials, with actuation controlled by piezoelectric motors and optical encoders. The needle guide hangs between independent front and rear two-link arms, which allows for horizontal and vertical translation as well as pitch and yaw rotation of the guide with a 6.0 cm range of motion in each direction. Needles are inserted manually through a chosen hole in the guide, which has been aligned with the target in the prostate. Open-air positioning error was evaluated using an optical tracking system (0.25 mm RMS accuracy) to measure 125 trajectories in free space. Correction of systematic bias in the system was performed using 85 of the trajectories, and the remaining 40 were used to estimate the residual error. The error was calculated as the horizontal and vertical displacement between the axis of the desired and measured trajectories at a typical needle insertion depth of 10 cm. MR-compatibility was evaluated using a grid phantom to assess image degradation due to the presence of the system, and induced force, heating, and electrical interference in the system were assessed qualitatively. In-bore positioning error was evaluated on 25 trajectories. RESULTS: Open-air mean positioning error at the needle tip was 0.80 ± 0.36 mm with a one-sided 95% confidence interval of 1.40 mm. The mean deviation of needle trajectories from the planned direction was 0.14 ± 0.06∘ . In the MR bore, the mean positioning error at the needle tip was 2.11 ± 1.05 mm with a one-sided 95% prediction interval of 3.84 mm. The mean angular error was 0.49 ± 0.26∘ . The system was found to be compatible with the MR environment under the specified gradient-echo sequence parameters used in this study. CONCLUSION: A complete system for delivering needles to localized prostate tumors was developed and described in this work, and its compatibility with the MR environment was demonstrated. In-bore MRI positioning error was sufficiently small for targeting small localized prostate tumors.

Clostridioides (Clostridium) difficile in neonatal foals and mares at a referral hospital.

BACKGROUND: Understanding the epidemiology of Clostridium difficile is important for the development and assessment of infection prevention and control practices, as well as surveillance methods and interpretation of diagnostic testing results. OBJECTIVE: Our objective was to longitudinally evaluate C. difficile shedding in neonatal foals and mares admitted to a referral hospital neonatal intensive care unit. ANIMALS: Foals admitted to a neonatal intensive care unit, along with their dams. METHODS: Rectal swabs were collected from mares and foals at admission, and then approximately every 3 days, when possible. Selective culture for C. difficile was performed and isolates were characterized by toxin gene PCR and ribotyping. RESULTS: Clostridium difficile was isolated from 103/409 (25%) samples; 65/208 (31%) from foals and 38/201 (19%) from mares. Cumulatively, C. difficile was isolated from at least 1 sample from 50/113 (44%) foals and 30/97 (31%) mares. No association was found between hospitalization day and isolation of C. difficile (P = .13). Twenty-three different ribotypes were identified, with ribotype 078 predominating. Fifteen foals had 2 positive samples during hospitalization. In only 6/15 (40%) foals was the same strain identified both times (5 ribotype 078 and 1 ribotype 012). CONCLUSIONS AND CLINICAL IMPORTANCE: Clostridium difficile is an important pathogen in adult horses and foals, and our findings highlight the complexity surrounding the epidemiology of this opportunistic pathogen. It can be found commonly, transiently, and cluster within a facility in the absence of identifiable disease occurrences or clusters.

The Event-Specific Benefits of Writing About a Difficult Life Experience.

Previous research demonstrates that writing about life's difficult moments benefits the writer cognitively and emotionally. However, it is unclear whether the benefits of writing are specific to the event written about or whether the benefits are global. This study was designed to address this issue. Participants were 120 undergraduate students who had experienced at least two difficult life events. Participants were randomly assigned into experimental and control groups. Experimental participants wrote about one of these difficult events and control participants wrote about an interesting life event of their choosing. Experimental participants reported their positive and negative emotions as well as their cognitive avoidance and intrusion concerning the event written about and another event not written about. Control participants reported their emotions and cognitions concerning two difficult life events. All participants also reported their general distress. These assessments were done immediately after writing and one week later. The results indicated that experimental participants were emotionally stronger, less upset, and less cognitively avoidant about the particular difficult life event they wrote about compared to an event they did not write about. Similar comparisons between ratings of a written-about and a not-written-about event were not significant for passion, fear, and cognitive intrusion. There was evidence for a possible indirect effect of writing on general distress through changes in event-specific cognitions and emotions. Discussion of these results focuses on how writing may specifically help change a writer's feelings and thoughts about a particular situation.

Development of a mechatronic guidance system for targeted ultrasound-guided biopsy under high-resolution positron emission mammography localization.

PURPOSE: Image-guided needle biopsy of small, detectable lesions is crucial for early-stage diagnosis, treatment planning, and management of breast cancer. High-resolution positron emission mammography (PEM) is a dedicated functional imaging modality that can detect breast cancer independent of breast tissue density, but anatomical context and real-time needle visualization are not yet available to guide biopsy. We propose a mechatronic guidance system integrating an ultrasound (US)-guided core-needle biopsy (CNB) with high-resolution PEM localization to improve the spatial sampling of breast lesions. This paper presents the benchtop testing and phantom studies to evaluate the accuracy of the system and its constituent components for targeted PEM-US-guided biopsy under simulated high-resolution PEM localization. METHODS: A mechatronic guidance system was developed to operate with the Radialis PEM system and a conventional US system. The system includes a user-operated guidance arm and end-effector biopsy device, integrating a US transducer and CNB gun, with its needle focused on a remote center of motion (RCM). Custom software modules were developed to track, display, and guide the end-effector biopsy device. Registration of the mechatronic guidance system to a simulated PEM detector plate was performed using a landmark-based method. Testing was performed with fiducials positioned in the peripheral and central regions of the simulated detector plate and registration error was quantified. Breast phantom experiments were performed under ideal detection and localization to evaluate for bias in the end-effector biopsy device. The accuracy of the complete mechatronic guidance system to perform targeted breast biopsy was assessed using breast phantoms with simulated lesions. Three-dimensional positioning error was quantified, and principal component analysis assessed for directional trends in 3D space within 95% prediction intervals. Targeted breast biopsies with test phantoms were performed and an overall in-plane needle targeting error was quantified. RESULTS: The mean registration errors were 0.63 mm (N = 44) and 0.73 mm (N = 72) in the peripheral and central regions of the simulated PEM detector plate, respectively. A 3D 95% prediction ellipsoid shows an error volume <2.0 mm in diameter, centered on the mean registration error. Under ideal detection and localization, targets <1.0 mm in diameter can be sampled with 95% confidence. The complete mechatronic guidance system was able to successfully spatially sample simulated breast lesions, 4 mm and 6 mm in diameter and height (N = 20) in known 3D positions in the PEM image coordinate space. The 3D positioning error was 0.85 mm (N = 20) with 0.64 mm in-plane and 0.44 mm cross-plane component errors. Targeted breast biopsies resulted in a mean in-plane needle targeting error of 1.08 mm (N = 15) allowing for targets 1.32 mm in radius to be sampled with 95% confidence. CONCLUSIONS: We demonstrated the utility of our mechatronic guidance system for targeted breast biopsy under high-resolution PEM localization. Breast phantom studies showed the ability to accurately guide, position, and target breast lesions with the accuracy to spatially sample targets <3.0 mm in diameter with 95% confidence. Future work will integrate the developed system with the Radialis PEM system toward combined PEM-US-guided breast biopsy.