Characterization of blue-green blood leukocyte inclusions and accompanying clinical, hematologic, and serum biochemical changes in dogs.

BACKGROUND: Lipofuscin-like cytoplasmic inclusions have been reported in human blood neutrophils and monocytes but have not been described in dogs. In people, these "green granules of death" have been associated with moderate to severe hepatocellular injury and high mortality. OBJECTIVES: To describe clinicopathologic abnormalities, diagnoses, and outcomes of dogs with greenish inclusions in blood neutrophils or monocytes, and to determine if the inclusions have features of lipofuscin. METHODS: Clinical cases were identified prospectively through routine evaluation of CBC samples. Leukocyte inclusions were characterized with routine staining and assessed for iron and autofluorescence. Additional cases were identified by examination of archived blood smears from dogs meeting search criteria for hepatocellular injury, and clinicopathologic findings were recorded. RESULTS: All 7 prospectively identified dogs with inclusions had inflammation and moderate to marked increases in serum alanine aminotransferase (ALT) activity, as did the 4 dogs identified from the 97 meeting retrospective search criteria. The inclusions were Prussian blue-negative (5/5) with broad-spectrum autofluorescence (5/5) and the appearance of lipofuscin with and without Wright staining. Most clinical diagnoses involved hepatic disorders (5/7 prospective and 3/4 retrospective cases) or pancreatitis (3/7 prospective and 2/4 retrospective cases), and some involved both; 8 of 11 dogs died within 7 days of admission. CONCLUSIONS: Blue-green cytoplasmic inclusions uncommonly found in blood neutrophils ± monocytes of routine canine blood smears have stained and unstained properties of lipofuscin and suggest the presence of hepatocellular injury, often severe. Reporting these inclusions is recommended to guide clinical management.

Conduction System Pacing in Pediatrics and Congenital Heart Disease: A Case Report and Literature Review.

Conduction system pacing involving either His bundle pacing (HBP) or left bundle branch pacing (LBBP) is a modality that has been introduced as a safe and effective alternative to right ventricular (RV) pacing to help prevent pacemaker-associated cardiomyopathy. While HBP has been employed in the pediatric and congenital populations, several small studies have shown LBBP to be safe and effective in the pediatric population. We present a patient with congenital atrioventricular block and postoperative ventricular septal defect repair cardiomyopathy with subsequent left ventricular function improvement following a transition from an RV epicardial pacemaker system to an LBBP system. This case report serves as a foundation for a review of the current state of LBBP in pediatrics and congenital heart disease.

Evaluation of medication safety assessment tools for pharmacist-led medication reviews: the Eastern European pilot project.

Background: Pharmacist-led medication reviews (MR) are one of the key methods to support medication safety in polypharmacy patients. The aims of this study were to pilot MRs in Eastern European community pharmacies, describe medication use in polypharmacy patients, and evaluate the usability of medication safety assessment tools. Methods: The MR pilot was undertaken in Estonia, Latvia, Poland, Hungary, Romania, and Bulgaria. Patients who used at least five medicines were directed to the service by their GPs. Data on drug-related problems (DRPs) and adherence were collected by pharmacists through structured patient interviews. Databases for identification of potential drug-drug interactions (pDDIs) and adverse drug reactions (ADRs) named Inxbase/Riskbase, as well as an integrated tool comprising potentially inappropriate medicines (PIMs) lists EU(7)-PIM and EURO-FORTA, were applied retroactively to the MR pilot data to investigate possibilities for their use and to describe medication use and potential risks in the study population. Results: A total of 318 patients were included in the study, 250 of them elderly (≥65 years). One hundred and eighty (56.6%) participants had a total of 504 pDDIs based on Inxbase analysis. On average, there were 1.6 pDDIs per participant. Twenty-five (5.0%) of the 504 pDDIs were in a high-risk category. A total of 279 (87.7%) participants had a potential ADR in at least one of 10 Riskbase categories. One hundred and fifty-four (20.8%) of the potential ADRs were in a high-risk category. Twenty-seven pDDIs and 68 ADRs documented as DRPs during the service were not included in the databases. Using the integrated EU(7)-PIM/EURO-FORTA PIM list, a total of 816 PIMs were found in 240 (96%) of the 250 elderly participants (on average 3.4 PIMs per elderly participant). Seventy-one (29.6%) of the participants were using high-risk PIMs. Twenty-one percent of high-risk PIMs and 13.8% of medium-risk PIMs were documented as DRPs by the pharmacists during the pilot. Conclusion: Medication safety assessment tools can be useful in guiding decision-making during MRs; however, these tools cannot replace patient interviews and monitoring. Tools that include a thorough explanation of the potential risks and are easy to use are more beneficial for MRs.

Multiyear Interval Changes in Aortic Wall Shear Stress in Patients with Bicuspid Aortic Valve Assessed by 4D Flow MRI.

BACKGROUND: In patients with bicuspid aortic valve (BAV), 4D flow MRI can quantify regions exposed to abnormal aortic hemodynamics, including high wall shear stress (WSS), a known stimulus for arterial wall dysfunction. However, the long-term multiscan reproducibility of 4D flow MRI-derived hemodynamic parameters is unknown. PURPOSE: To investigate the long-term stability of 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps in patients with BAV undergoing multiyear surveillance imaging. STUDY TYPE: Retrospective. POPULATION: 20 BAV patients (mean age 48.4 ± 13.9 years; 14 males) with five 4D flow MRI scans, with intervals of at least 6 months between scans, and 125 controls (mean age: 50.7 ± 15.8 years; 67 males). FIELD STRENGTH/SEQUENCE: 1.5 and 3.0T, prospectively ECG and respiratory navigator-gated aortic 4D flow MRI. ASSESSMENT: Automated AI-based 4D flow analysis pipelines were used for data preprocessing, aorta 3D segmentation, and quantification of ascending aorta (AAo) peak velocity, peak systolic WSS, and heatmap-derived relative area of elevated WSS compared to WSS ranges in age and sex-matched normative control populations. Growth rate was derived from the maximum AAo diameters measured on the first and fifth MRI scans. STATISTICAL TESTS: One-way repeated measures analysis of variance. P < 0.05 indicated significance. RESULTS: One hundred 4D flow MRI exams (five per patient) were analyzed. The mean total follow-up duration was 5.5 ± 1.1 years, and the average growth rate was 0.3 ± 0.2 mm/year. Peak velocity, peak systolic WSS, and relative area of elevated WSS did not change significantly over the follow-up period (P = 0.64, P = 0.69, and P = 0.35, respectively). The patterns and areas of elevated WSS demonstrated good reproducibility on semiquantitative assessment. CONCLUSION: 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps showed good multiyear and multiscan stability in BAV patients with low aortic growth rates. These findings underscore the reliability of these metrics in monitoring BAV patients for potential risk of dilation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Gametic selection favours polyandry and selfing.

Competition among pollen or sperm (gametic selection) can cause evolution. Mating systems shape the intensity of gametic selection by determining the competitors involved, which can in turn cause the mating system itself to evolve. We model the bidirectional relationship between gametic selection and mating systems, focusing on variation in female mating frequency (monandry-polyandry) and self-fertilisation (selfing-outcrossing). First, we find that monandry and selfing both reduce the efficiency of gametic selection in removing deleterious alleles. This means that selfing can increase mutation load, in contrast to cases without gametic selection where selfing purges deleterious mutations and decreases mutation load. Second, we explore how mating systems evolve via their effect on gametic selection. By manipulating gametic selection, polyandry can evolve to increase the fitness of the offspring produced. However, this indirect advantage of post-copulatory sexual selection is weak and is likely to be overwhelmed by any direct fitness effects of mating systems. Nevertheless, gametic selection can be potentially decisive for selfing evolution because it significantly reduces inbreeding depression, which favours selfing. Thus, the presence of gametic selection could be a key factor driving selfing evolution.

The paternal role in pregnancy loss.

In this comprehensive review, the intricate relationship between paternal factors and pregnancy loss is examined. While pregnancy loss has historically been predominantly attributed to maternal factors, recent research underscores the significant contribution of the male partner. The review delves into various aspects of paternal influence, including paternal age, health, chromosome abnormalities, Y chromosome deletions, and sperm DNA fragmentation. Notably, advanced paternal age is found to be associated with an increased risk of recurrent pregnancy loss, shedding light on the importance of understanding the impact of aging on male fertility. Additionally, paternal health, particularly metabolic syndrome, emerges as a noteworthy factor contributing to pregnancy loss. Chromosome abnormalities in male partners, such as balanced translocations, and Y chromosome microdeletions are explored in the context of pregnancy loss risk. Moreover, the review highlights the growing body of evidence linking sperm DNA fragmentation and sperm protein abnormalities to spontaneous pregnancy loss, emphasizing the significance of sperm health in reproductive outcomes. Overall, this review provides a comprehensive overview of the multifaceted role of the male partner in pregnancy loss, calling for a more inclusive approach to pregnancy loss investigations that encompasses both maternal and paternal factors.

Cytokine Release by Microglia Exposed to Neurologic Injury Is Amplified by Lipopolysaccharide.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and morbidity in the trauma population. Microglia drive the secondary neuroinflammatory response after TBI. We sought to determine if the microglial response to neurologic injury was exacerbated by a second stimulus after exposure to neurologic injury. METHODS: Sprague-Dawley rats (age 2-3 wk) were divided into injured and noninjured groups. Injured rats underwent a controlled cortical impact injury; noninjured rats remained naïve to any injury and served as the control group. Primary rat microglia were isolated and applied to in vitro cultures. After incubation for 24 h, the microglia were stimulated with lipopolysaccharide (LPS) or norepinephrine. Twenty-four hours after stimulation, cell culture supernatant was collected. Tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) production were measured by standard enzyme-linked immunosorbent assays. GraphPad Prism was used for statistical analysis. RESULTS: When compared to noninjured microglia, LPS induced a significantly greater production of TNF-α in microglia isolated from the injured ipsilateral (versus noninjured = 938.8 ± 155.1, P < 0.0001) and injured contralateral hemispheres (versus noninjured = 426.6 ± 155.1, P < 0.0001). When compared to microglia from noninjured cerebral tissue, IL-6 production was significantly greater after LPS stimulation in the injured ipsilateral hemisphere (mean difference versus noninjured = 9540 ± 3016, P = 0.0101) and the contralateral hemisphere (16,700 ± 3016, P < 0.0001). Norepinephrine did not have a significant effect on IL-6 or TNF-α production. CONCLUSIONS: LPS stimulation may amplify the release of proinflammatory cytokines from postinjury microglia. These data suggest that post-TBI complications, like sepsis, may propagate neuroinflammation by augmenting the proinflammatory response of microglia.

Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural central nervous system preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at 2 children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation, and infusion were completed by 48 hours post-injury. Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between 2 doses. Primary endpoints were quantitative brain volumes using magnetic resonance imaging and microstructural integrity of the corpus callosum (CC; diffusivity and edema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days, and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring, and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo (decrease of 19891 vs 40491, respectively; mean difference of -20600, 95% CI: -35868 to -5332; P = 0.01), and the number of CC streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved CC connectivity in the treated groups (-431 streamlines placebo vs. -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 hours after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to 1) shorter intensive care duration and decreased ICU intensity; 2) white matter structural preservation; and 3) enhanced CC connectivity and improved microstructural metrics.

Perioperative Patients With Hemodynamic Instability: Consensus Recommendations of the Anesthesia Patient Safety Foundation.

In November of 2022, the Anesthesia Patient Safety Foundation held a Consensus Conference on Hemodynamic Instability with invited experts. The objective was to review the science and use expert consensus to produce best practice recommendations to address the issue of perioperative hemodynamic instability. After expert presentations, a modified Delphi process using discussions, voting, and feedback resulted in 17 recommendations regarding advancing the perioperative care of the patient at risk of, or with, hemodynamic instability. There were 17 high-level recommendations. These recommendations related to the following 7 domains: Current Knowledge (5 statements); Preventing Hemodynamic Instability-Related Harm During All Phases of Care (4 statements); Data-Driven Quality Improvement (3 statements); Informing Patients (2 statements); The Importance of Technology (1 statement); Launch a National Campaign (1 statement); and Advancing the Science (1 statement). A summary of the recommendations is presented in Table 1 .

Combatting SARS-CoV-2 With Digital Contact Tracing and Notification: Navigating Six Points of Failure.

Digital contact tracing and notification were initially hailed as promising strategies to combat SARS-CoV-2; however, in most jurisdictions, they did not live up to their promise. To avert a given transmission event, both parties must have adopted the technology, it must detect the contact, the primary case must be promptly diagnosed, notifications must be triggered, and the secondary case must change their behavior to avoid the focal tertiary transmission event. If we approximate these as independent events, achieving a 26% reduction in the effective reproduction number Rt would require an 80% success rate at each of these 6 points of failure. Here, we review the 6 failure rates experienced by a variety of digital contact tracing and contact notification schemes, including Singapore's TraceTogether, India's Aarogya Setu, and leading implementations of the Google Apple Exposure Notification system. This leads to a number of recommendations, for example, that the narrative be framed in terms of user autonomy rather than user privacy, and that tracing/notification apps be multifunctional and integrated with testing, manual contact tracing, and the gathering of critical scientific data.

Residential Mobility and Reasons for Moving Among People Living With Spinal Cord Injury: Results of a Multisite Survey Study.

Background: Residential mobility after spinal cord injury (SCI) has not been extensively examined despite a growing interest in investigating the relationship between neighborhood exposures and community living outcomes. Objectives: This study explores residential mobility patterns, the annual move rate, and reasons for moving among a community-living sample of adults with SCI. Methods: A survey was conducted with 690 people at six SCI Model Systems centers in the United States between July 2017 and October 2020. The outcomes included move status in the past 12 months, move distance, and the primary reason for moving. A sample from the 2019 American Community Survey (ACS) 5-year pooled estimates was obtained for comparative analysis. Descriptive statistics were used to summarize the distributions of the outcomes and differences between the samples. Results: The annual move rate for adults with SCI was 16.4%, and most moves were within the same county (56.6%). Recent movers were more likely to be young adults, be newly injured, and have low socioeconomic status. Housing quality, accessibility, and family were more frequently reported motivations for moving compared to employment. Young adults more commonly moved for family and accessibility, whereas middle-aged adults more commonly moved for housing quality. No notable difference was observed in the annual move rate between the SCI and the general population samples. Conclusion: These findings suggest an age-related pattern of residential relocation after SCI, which may be indicative an extended search for optimal living conditions that meet the housing and accessibility needs of this population.

Antimicrobial prescribing in a secondary care setting during the COVID-19 pandemic.

Background: Increased antimicrobial resistance patterns lead to limited options for antimicrobial agents, affecting patient health and increasing hospital costs. Objectives: To investigate the antimicrobial prescribing patterns at two district hospitals in Northern Ireland before and during the COVID-19 pandemic. Methods: A mixed prospective-retrospective study was designed to compare pre- and during pandemic antimicrobial prescribing data in both hospitals using a Global Point Prevalence Survey. Results: Of the 591 patients surveyed in both hospitals, 43.8% were treated with 402 antimicrobials. A total of 82.8% of antimicrobial prescriptions were for empirical treatment. No significant difference existed in numbers of patients treated or antimicrobials used before and during the pandemic. There was a slight decrease of 3.3% in the compliance rate with hospital antimicrobial guidelines during the pandemic when compared with the pre-pandemic year of 2019, when it was 69.5%. Treatment based on patients' biomarker data also slightly decreased from 83.5% pre-pandemic (2019) to 81.5% during the pandemic (2021). Conclusions: There was no overall significant impact of the pandemic on the antimicrobial prescribing patterns in either hospital when compared with the pre-pandemic findings. The antimicrobial stewardship programmes would appear to have played an important role in controlling antimicrobial consumption during the pandemic.

Impact of Holocene environmental change on the evolutionary ecology of an Arctic top predator.

The Arctic is among the most climatically sensitive environments on Earth, and the disappearance of multiyear sea ice in the Arctic Ocean is predicted within decades. As apex predators, polar bears are sentinel species for addressing the impact of environmental variability on Arctic marine ecosystems. By integrating genomics, isotopic analysis, morphometrics, and ecological modeling, we investigate how Holocene environmental changes affected polar bears around Greenland. We uncover reductions in effective population size coinciding with increases in annual mean sea surface temperature, reduction in sea ice cover, declines in suitable habitat, and shifts in suitable habitat northward. Furthermore, we show that west and east Greenlandic polar bears are morphologically, and ecologically distinct, putatively driven by regional biotic and genetic differences. Together, we provide insights into the vulnerability of polar bears to environmental change and how the Arctic marine ecosystem plays a vital role in shaping the evolutionary and ecological trajectories of its inhabitants.

Valvular and ascending aortic hemodynamics of the On-X aortic valved conduit by same-day echocardiography and 4D flow MRI.

This study aims to assess whether the On-X aortic valved conduit better restores normal valvular and ascending aortic hemodynamics than other commonly used bileaflet mechanical valved conduit prostheses from St. Jude Medical and Carbomedics by using same-day transthoracic echocardiography (TTE) and 4D flow magnetic resonance imaging (MRI) examinations. TTE and 4D flow MRI were performed back-to-back in 10 patients with On-X, six patients with St. Jude (two) and Carbomedics (four) prostheses, and 36 healthy volunteers. TTE evaluated valvular hemodynamic parameters: transvalvular peak velocity (TPV), mean and peak transvalvular pressure gradient (TPG), and effective orifice area (EOA). 4D flow MRI evaluated the peak systolic 3D viscous energy loss rate (VELR) density and mean vorticity magnitude in the ascending aorta (AAo). While higher TPV and mean and peak TPG were recorded in all patients compared to healthy subjects, the values in On-X patients were closer to those in healthy subjects (TPV 1.9 ± 0.3 vs. 2.2 ± 0.3 vs. 1.2 ± 0.2 m/s, mean TPG 7.4 ± 1.9 vs. 9.2 ± 2.3 vs. 3.1 ± 0.9 mmHg, peak TPG 15.3 ± 5.2 vs. 18.9 ± 5.2 vs. 6.1 ± 1.8 mmHg, p < 0.001). Likewise, while higher VELR density and mean vorticity magnitude were recorded in all patients than in healthy subjects, the values in On-X patients were closer to those in healthy subjects (VELR: 50.6 ± 20.1 vs. 89.8 ± 35.2 vs. 21.4 ± 9.2 W/m3, p < 0.001) and vorticity (147.6 ± 30.0 vs. 191.2 ± 26.0 vs. 84.6 ± 20.5 s-1, p < 0.001). This study demonstrates that the On-X aortic valved conduit may produce less aberrant hemodynamics in the AAo while maintaining similar valvular hemodynamics to St. Jude Medical and Carbomedics alternatives.

PET imaging of microglia using PBR28suv determines therapeutic efficacy of autologous bone marrow mononuclear cells therapy in traumatic brain injury.

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI.

Family-Centered Interventions for Children on the Autism Spectrum (2013-2021).

Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. The authors completed a systematic review of family- and person-centered planning interventions for families of autistic1 children, or autistic adolescents and adults gathered from literature published between 2013 and 2021. This systematic review brief presents findings from the six included articles that focused on family-centered planning interventions. Emerging evidence from these six studies supports the use of coaching interventions with caregivers of children on the autism spectrum to address both child and parent outcomes. These outcomes include individualized goals; caregiver sense of competence, empowerment, or self-efficacy; occupational performance of children and mothers; and caregiver satisfaction with their child's occupational performance.

Person-Centered Interventions for Autistic Adults Ages 18+ (2013-2021).

Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence for a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adults aged 18+ years gathered from literature published between 2013 and 2021.

Clinical pharmacy interventions in an Austrian hospital: a report highlights the need for the implementation of clinical pharmacy services.

BACKGROUND: Clinical pharmacy services face challenges in Austria due to limited implementation and acceptance, outdated legislation and a lack of guidelines and training, despite the evidence from global studies of the positive impact of clinical pharmacists on patient care. OBJECTIVES: First, to identify the necessary types of clinical pharmacy interventions required at a 360-bed hospital located in Austria. Second, to evaluate the extent to which physicians accept the suggestions made by clinical pharmacists. METHODS: Over a period of 27 months, a clinical pharmacist made a series of interventions, which were evaluated using a six-point clinical significance scale. To determine the inter-rater reliability, a subset of 25 interventions was assessed for their clinical significance by four independent internal medicine physicians. RESULTS: A total of 1064 interventions were made by the pharmacist. Clinical pharmacy input was deemed necessary for 986 out of 1364 (72.3%) patients, with an average of 1.08 interventions per patient. The prompt acceptance rate of these interventions by physicians was 83.5% (888/1064), while 12.9% (137/1064) were considered by physicians but not immediately acted upon. The average clinical significance intervention rating was 2.15. The inter-rater reliability agreement between the four MDs and between the four MDs and the pharmacist was classified as 'good' to 'moderate'. CONCLUSION: This study in a secondary care Austrian hospital demonstrates the requirement for clinical pharmacy services, which are highly valued by other healthcare professionals. The clinical pharmacist is a key member of the multidisciplinary ward team, playing a vital role in reducing drug-related problems and enhancing patient safety. This work should now be scaled and tested in other Austrian hospitals.