Dual thermal ecotypes coexist within a nearly genetically identical population of the unicellular marine cyanobacterium Synechococcus.

The extent and ecological significance of intraspecific functional diversity within marine microbial populations is still poorly understood, and it remains unclear if such strain-level microdiversity will affect fitness and persistence in a rapidly changing ocean environment. In this study, we cultured 11 sympatric strains of the ubiquitous marine picocyanobacterium Synechococcus isolated from a Narragansett Bay (RI) phytoplankton community thermal selection experiment. Thermal performance curves revealed selection at cool and warm temperatures had subdivided the initial population into thermotypes with pronounced differences in maximum growth temperatures. Curiously, the genomes of all 11 isolates were almost identical (average nucleotide identities of >99.99%, with >99% of the genome aligning) and no differences in gene content or single nucleotide variants were associated with either cool or warm temperature phenotypes. Despite a very high level of genomic similarity, sequenced epigenomes for two strains showed differences in methylation on genes associated with photosynthesis. These corresponded to measured differences in photophysiology, suggesting a potential pathway for future mechanistic research into thermal microdiversity. Our study demonstrates that present-day marine microbial populations can harbor cryptic but environmentally relevant thermotypes which may increase their resilience to future rising temperatures.

Phytoplankton thermal trait parameterization alters community structure and biogeochemical processes in a modeled ocean.

Phytoplankton exhibit diverse physiological responses to temperature which influence their fitness in the environment and consequently alter their community structure. Here, we explored the sensitivity of phytoplankton community structure to thermal response parameterization in a modelled marine phytoplankton community. Using published empirical data, we evaluated the maximum thermal growth rates (µmax ) and temperature coefficients (Q10 ; the rate at which growth scales with temperature) of six key Phytoplankton Functional Types (PFTs): coccolithophores, cyanobacteria, diatoms, diazotrophs, dinoflagellates, and green algae. Following three well-documented methods, PFTs were either assumed to have (1) the same µmax and the same Q10 (as in to Eppley, 1972), (2) a unique µmax but the same Q10 (similar to Kremer et al., 2017), or (3) a unique µmax and a unique Q10 (following Anderson et al., 2021). These trait values were then implemented within the Massachusetts Institute of Technology biogeochemistry and ecosystem model (called Darwin) for each PFT under a control and climate change scenario. Our results suggest that applying a µmax and Q10 universally across PFTs (as in Eppley, 1972) leads to unrealistic phytoplankton communities, which lack diatoms globally. Additionally, we find that accounting for differences in the Q10 between PFTs can significantly impact each PFT's competitive ability, especially at high latitudes, leading to altered modeled phytoplankton community structures in our control and climate change simulations. This then impacts estimates of biogeochemical processes, with, for example, estimates of export production varying by ~10% in the Southern Ocean depending on the parameterization. Our results indicate that the diversity of thermal response traits in phytoplankton not only shape community composition in the historical and future, warmer ocean, but that these traits have significant feedbacks on global biogeochemical cycles.

Pregnancy and assisted reproductive technology use in Australian female transfusion-dependent haemoglobinopathy patients: a 20-year retrospective analysis.

BACKGROUND: In the last few decades, the life expectancy of patients with transfusion-dependent thalassaemia (TDT) and sickle cell disease (SCD) has improved significantly, in part because of improved iron chelation. Fertility challenges and pregnancy complications have historically limited reproductive options in this group; however, improved multi-disciplinary care has made infertility a chronic disease complication requiring attention. Despite this, there are very few reports and no Australian data describing fertility and pregnancy outcomes in this population. AIMS: To identify the rate of assisted reproductive technologies (ART) utilisation in our female transfusion-dependent haemoglobinopathy patients and to establish the nature of maternal and neonatal complications in this cohort. METHODS: A 20-year retrospective analysis (1997-2017) at an Australian centre captured data on conception rates, use of assisted reproductive techniques (ART), and pregnancy and neonatal outcomes in female transfusion-dependent haemoglobinopathy patients. RESULTS: Conception was attempted in 14 women (11 TDT and three SCD) during the study period. A total of 28 pregnancies resulting in 25 live births were recorded. ART supported 13 conceptions. A positive association was not identified between elevated mean serum ferritin and ART use; however, all patients with an established diagnosis of hypogonadotropic hypogonadism (HH) required ART. Maternal complications included gestational diabetes mellitus and post-partum haemorrhage. There were no cardiac complications. Two-thirds of women underwent lower segment caesarean section, with prematurity complicating 20% of births. There were no neonatal or maternal deaths. CONCLUSION: Pregnancy is an achievable goal for women with transfusion-dependent haemoglobinopathies, although the support of ART may be required in a subset of patients.

A novel, cassette-based nitric oxide delivery system with an advanced feedback control algorithm accurately delivers nitric oxide via the anesthesia machine independent of fresh gas flow rate and volatile anesthetic agent.

Nitric oxide (NO), a selective pulmonary vasodilator, can be delivered via conventional ICU and anesthesia machine ventilators. Anesthesia machines are designed for rebreathing of circulating gases, reducing volatile anesthetic agent quantity used. Current cylinder- and ionizing-based NO delivery technologies use breathing circuit flow to determine NO delivery and do not account for recirculated gases; therefore, they cannot accurately dose NO at FGF below patient minute ventilation (MV). A novel, cassette-based NO delivery system (GENOSYL® DS, Vero Biotech Inc.) uses measured NO concentration in the breathing circuit as an input to an advanced feedback control algorithm, providing accurate NO delivery regardless of FGF and recirculation of gases. This study evaluated GENOSYL® DS accuracy with different anesthesia machines, ventilation parameters, FGFs, and volatile anesthetics. GENOSYL® DS was tested with GE Aisys and Dräger Fabius anesthesia machines to determine NO dose accuracy with FGF < patient MV, and with a Getinge Flow-i anesthesia machine to determine NO dose accuracy when delivering various volatile anesthetic agents. Neonatal and adult mechanical ventilation parameters and circuits were used. GENOSYL® DS maintained accurate NO delivery with all three anesthesia machines, at low FGF with recirculation of gases, and with all volatile anesthetic agents at different concentrations. Measured NO2 levels remained acceptable at ≤ 1 ppm with set NO dose ≤ 40 ppm. GENOSYL® DS, with its advanced feedback control algorithm, is the only NO delivery system capable of accurately dosing NO with anesthesia machines with rebreathing ventilation parameters (FGF < MV) regardless of anesthetic agent.

Thermal trait variation may buffer Southern Ocean phytoplankton from anthropogenic warming.

Despite the potential of standing genetic variation to rescue communities and shape future adaptation to climate change, high levels of uncertainty are associated with intraspecific trait variation in marine phytoplankton. Recent model intercomparisons have pointed to an urgent need to reduce uncertainty in the projected responses of marine ecosystems to climate change, including Southern Ocean (SO) surface waters, which are among the most rapidly warming habitats on Earth. Because SO phytoplankton growth responses to warming sea surface temperature (SST) are poorly constrained, we developed a high-throughput growth assay to simultaneously examine inter- and intra-specific thermal trait variation in a group of 43 taxonomically diverse and biogeochemically important SO phytoplankton called diatoms. We found significant differential growth performance among species across thermal traits, including optimum and maximum tolerated growth temperatures. Within species, coefficients of variation ranged from 3% to 48% among strains for those same key thermal traits. Using SO SST projections for 2100, we predicted biogeographic ranges that differed by up to 97% between the least and most tolerant strains for each species, illustrating the role that strain-specific differences in temperature response can play in shaping predictions of future phytoplankton biogeography. Our findings revealed the presence and scale of thermal trait variation in SO phytoplankton and suggest these communities may already harbour the thermal trait diversity required to withstand projected 21st-century SST change in the SO even under severe climate forcing scenarios.

Hyperpolarized 13 C magnetic resonance imaging for noninvasive assessment of tissue inflammation.

Inflammation is a central mechanism underlying numerous diseases and incorporates multiple known and potential future therapeutic targets. However, progress in developing novel immunomodulatory therapies has been slowed by a need for improvement in noninvasive biomarkers to accurately monitor the initiation, development and resolution of immune responses as well as their response to therapies. Hyperpolarized magnetic resonance imaging (MRI) is an emerging molecular imaging technique with the potential to assess immune cell responses by exploiting characteristic metabolic reprogramming in activated immune cells to support their function. Using specific metabolic tracers, hyperpolarized MRI can be used to produce detailed images of tissues producing lactate, a key metabolic signature in activated immune cells. This method has the potential to further our understanding of inflammatory processes across different diseases in human subjects as well as in preclinical models. This review discusses the application of hyperpolarized MRI to the imaging of inflammation, as well as the progress made towards the clinical translation of this emerging technique.

Phase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours.

BACKGROUND: BAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents. METHODS: This two-part, open-label, phase 1/2a study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 2-h infusion of BAL101553 in adults with advanced or recurrent solid tumours. The MTD was determined using a modified accelerated titration design in phase I. Patients received BAL101553 at the MTD and at lower doses in the phase 2a expansion to characterise safety and efficacy and to determine the recommended phase 2 dose (RP2D). RESULTS: Seventy-three patients received BAL101553 at doses of 15-80 mg/m2 (phase 1, n = 24; phase 2a, n = 49). The MTD was 60 mg/m2; DLTs observed at doses ≥60 mg/m2 were reversible Grade 2-3 gait disturbance with Grade 2 peripheral sensory neuropathy. In phase 2a, asymptomatic myocardial injury was observed at doses ≥45 mg/m2. The RP2D for 2-h intravenous infusion was 30 mg/m2. The overall disease control rate was 26.3% in the efficacy population. CONCLUSIONS: The RP2D for 2-h infusion of BAL101553 was well tolerated. Dose-limiting neurological and myocardial side effects were consistent with the agent's vascular-disrupting properties. CLINICAL TRIAL REGISTRATION: EudraCT: 2010-024237-23.

CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels.

PURPOSE: Improved resolution of molecular diagnostic technologies enabled detection of smaller sized exonic level copy-number variants (CNVs). The contribution of CNVs to autosomal recessive (AR) conditions may be better recognized using a large clinical cohort. METHODS: We retrospectively investigated the CNVs' contribution to AR conditions in cases subjected to chromosomal microarray analysis (CMA, N = ~70,000) and/or clinical exome sequencing (ES, N = ~12,000) at Baylor Genetics; most had pediatric onset neurodevelopmental disorders. RESULTS: CNVs contributed to biallelic variations in 87 cases, including 81 singletons and three affected sibling pairs. Seventy cases had CNVs affecting both alleles, and 17 had a CNV and a single-nucleotide variant (SNV)/indel in trans. In total, 94.3% of AR-CNVs affected one gene; among these 41.4% were single-exon and 35.0% were multiexon partial-gene events. Sixty-nine percent of homozygous AR-CNVs were embedded in homozygous genomic intervals. Five cases had large deletions unmasking an SNV/indel on the intact allele for a recessive condition, resulting in multiple molecular diagnoses. CONCLUSIONS: AR-CNVs are often smaller in size, transmitted through generations, and underrecognized due to limitations in clinical CNV detection methods. Our findings from a large clinical cohort emphasized integrated CNV and SNV/indel analyses for precise clinical and molecular diagnosis especially in the context of genomic disorders.

CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms.

Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.

Detection of circulating tumour cell clusters in human glioblastoma.

Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular CTC clusters are generated in this disease and whether they can bypass the physical hurdle of the blood-brain barrier.  Here, we assessed CTC presence and composition at multiple time points in 13 patients with progressing GBM during an open-label phase 1/2a study with the microtubule inhibitor BAL101553. We observe CTC clusters ranging from 2 to 23 cells and present at multiple sampling time points in a GBM patient with pleomorphism and extensive necrosis, throughout disease progression. Exome sequencing of GBM CTC clusters highlights variants in 58 cancer-associated genes including ATM, PMS2, POLE, APC, XPO1, TFRC, JAK2, ERBB4 and ALK. Together, our findings represent the first evidence of the presence of CTC clusters in GBM.

Free text adversity statements as part of a contextualised admissions process: a qualitative analysis.

BACKGROUND: Medical schools globally are encouraged to widen access and participation for students from less privileged backgrounds. Many strategies have been implemented to address this inequality, but much still needs to be done to ensure fair access for all. In the literature, adverse circumstances include financial issues, poor educational experience and lack of professional-status parents. In order to take account of adverse circumstances faced by applicants, The University of Dundee School of Medicine offers applicants the opportunity to report circumstances which may have resulted in disadvantage. Applicants do this by completing a free text statement, known as an 'adversity statement', in addition to the other application information. This study analysed adversity statements submitted by applicants during two admissions cycles. Analysis of content and theme was done to identify the information applicants wished to be taken into consideration, and what range of adverse circumstances individuals reported. METHODS: This study used a qualitative approach with thematic analysis to categorise the adversity statements. The data was initially analysed to create a coding framework which was then applied to the whole data set. Each coded segment was then analysed for heterogeneity and homogeneity, segments merged into generated themes, or to create sub-themes. RESULTS: The data set comprised a total of 384 adversity statements. These showed a wide range of detail involving family, personal health, education and living circumstances. Some circumstances, such as geographical location, have been identified and explored in previous research, while others, such as long term health conditions, have had less attention in the literature. The degree of impact, the length of statement and degree of detail, demonstrated wide variation between submissions. CONCLUSIONS: This study adds to the debate on best practice in contextual admissions and raises awareness of the range of circumstances and impact applicants wish to be considered. The themes which emerged from the data included family, school, personal health, and geographical location issues. Descriptions of the degree of impact that an adverse circumstance had on educational or other attainment was found to vary substantially from statements indicating minor, impact through to circumstances stated as causing major impact.

Wide Variation and Overprescription of Opioids After Elective Surgery.

OBJECTIVE: We aimed to identify opioid prescribing practices across surgical specialties and institutions. BACKGROUND: In an effort to minimize the contribution of prescription narcotics to the nationwide opioid epidemic, reductions in postoperative opioid prescribing have been proposed. It has been suggested that a maximum of 7 days, or 200 mg oral morphine equivalents (OME), should be prescribed at discharge in opioid-naïve patients. METHODS: Adults undergoing 25 common elective procedures from 2013 to 2015 were identified from American College of Surgeons National Surgical Quality Improvement Program data from 3 academic centers in Minnesota, Arizona, and Florida. Opioids prescribed at discharge were abstracted from pharmacy data and converted into OME. Wilcoxon Rank-Sum and Kruskal-Wallis tests assessed variations. RESULTS: Of 7651 patients, 93.9% received opioid prescriptions at discharge. Of 7181 patients who received opioid prescriptions, a median of 375 OME (interquartile range 225-750) were prescribed. Median OME varied by sex (375 men vs 390 women, P = 0.002) and increased with age (375 age 18-39 to 425 age 80+, P < 0.001). Patients with obesity and patients with non-cancer diagnoses received more opioids (both P < 0.001). Subset analysis of the 5756 (75.2%) opioid-naïve patients showed the majority received >200 OME (80.9%). Significant variations in opioid prescribing practices were seen within each procedure and between the 3 medical centers. CONCLUSIONS: The majority of patients were overprescribed opioids. Significant prescribing variation exists that was not explained by patient factors. These data will guide practices to optimize opioid prescribing after surgery.

Developing a standardized healthcare cost data warehouse.

BACKGROUND: Research addressing value in healthcare requires a measure of cost. While there are many sources and types of cost data, each has strengths and weaknesses. Many researchers appear to create study-specific cost datasets, but the explanations of their costing methodologies are not always clear, causing their results to be difficult to interpret. Our solution, described in this paper, was to use widely accepted costing methodologies to create a service-level, standardized healthcare cost data warehouse from an institutional perspective that includes all professional and hospital-billed services for our patients. METHODS: The warehouse is based on a National Institutes of Research-funded research infrastructure containing the linked health records and medical care administrative data of two healthcare providers and their affiliated hospitals. Since all patients are identified in the data warehouse, their costs can be linked to other systems and databases, such as electronic health records, tumor registries, and disease or treatment registries. RESULTS: We describe the two institutions' administrative source data; the reference files, which include Medicare fee schedules and cost reports; the process of creating standardized costs; and the warehouse structure. The costing algorithm can create inflation-adjusted standardized costs at the service line level for defined study cohorts on request. CONCLUSION: The resulting standardized costs contained in the data warehouse can be used to create detailed, bottom-up analyses of professional and facility costs of procedures, medical conditions, and patient care cycles without revealing business-sensitive information. After its creation, a standardized cost data warehouse is relatively easy to maintain and can be expanded to include data from other providers. Individual investigators who may not have sufficient knowledge about administrative data do not have to try to create their own standardized costs on a project-by-project basis because our data warehouse generates standardized costs for defined cohorts upon request.

Episodic fevers and vasodilatory shock mimicking urosepsis in a patient with HIV-associated multicentric Castleman's Disease: a case report.

BACKGROUND: Multicentric Castleman's disease (MCD) is a pre-malignancy that presents with lymphadenopathy and features of systemic inflammation. Human immunodeficiency virus (HIV)-associated MCD is associated with human herpesvirus-8 (HHV-8) infection. If untreated MCD has a relapsing and remitting course that is eventually fatal. CASE PRESENTATION: A 67-year-old man had six hospital admissions over 20 months characterised by fever, urinary frequency and CRP >100 mg/L. The final admission was complicated by hypotension requiring intensive care unit admission and ionotropic support. His history included HIV and Hepatitis B virus (HBV) co-infection on suppressive therapy. Each presentation was managed as presumed urosepsis with use of empirical antibiotics, however numerous blood and urine cultures failed to identify a pathogen. A bone-marrow aspirate and trephine found no evidence of haematological malignancy. A positron emission tomography scan found active lymph nodes, one of which was biopsied and found to contain the plasma-cell variant of Castleman's disease. Ultimately the cause for the recurrent presentations was attributed to progressive MCD. The patient received rituximab monotherapy and has had no further related admissions. CONCLUSIONS: MCD should be considered in patients with chronic HIV infection presenting with recurrent sepsis-like episodes and/or vasodilatory shock, particularly if no pathogen is identified or lymphadenopathy is evident.

Implementing a community bullying awareness intervention in an adolescent psychiatric unit: a feasibility study.

PROBLEM: Adolescents with a mental health diagnosis are at risk of involvement in bullying. We tested the feasibility of a bullying awareness group intervention in an established inpatient psychiatric unit milieu. METHODS: Adolescents admitted to an urban inpatient adolescent psychiatric unit were eligible to attend two sequential 1-hour Bullying Awareness intervention group sessions. Data were collected before the first session (T1), post-both sessions (T2), and following discharge from the unit (T3). FINDINGS: A total of 65 adolescents were enrolled; most were female (66.2%), African-American (60%), and in grades 10 to 12 (57%). Intervention feasibility was achieved as >80% of participants completed all components of the intervention and 100% completed all study questionnaires at T1 and T2. Feasibility of the follow-up (T3) was not achieved. Bullying knowledge scores improved significantly from T1 to T2. CONCLUSIONS: The intervention is feasible to implement in an inpatient adolescent psychiatry unit and can improve adolescents' bullying knowledge.

Professionalism and Safety of DPT Students in First, Full-Time Clinical Experiences: Accelerated Hybrid versus Traditional Programs.

PURPOSE: Doctor of Physical Therapy (DPT) education continues to progress with contemporary content and innovative teaching methods. The purpose of this study was to examine clinical assessment data from the Physical Therapist Clinical Performance Instrument (PT-CPI) focused on professionalism and safety in an initial clinical experience between an accelerated-hybrid and traditional DPT program. METHODS: A retrospective analysis was performed on mid-term and final Safety, Professional Behavior, and Communication PT-CPI scores of each program's first clinical experience. The traditional program served as a control group. A total 186 students were examined: 100 from the traditional program and 86 from the accelerated-hybrid program. RESULTS: There was a significant effect of learning environment on final test scores while controlling for midterm scores in Safety (p < 0.001), Professional Behavior (p < 0.001), and Communication (p < 0.001) with students in the accelerated-hybrid program scoring higher. Each program showed improvements from midterm to final PT-CPI, outperforming the set benchmark score with the accelerated-hybrid program showing larger growth in Communication and Safety. CONCLUSION: Students in both DPT programs display acceptable levels of professionalism and safety according to program benchmarks and demonstrate growth in these areas throughout the clinical experiences despite differences in program design.

Early Oral Step-Down Versus Continued Intravenous Antibiotic Treatment of Complicated Intra-Abdominal Infection.

Background: Complicated intra-abdominal infections (cIAIs) require a combined tactic, of source control and antimicrobial therapy. This study aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial intravenous (IV) antimicrobial therapy. Methods: This retrospective cohort study included hospitalized adult patients diagnosed with a cIAI who received more than seven days of IV therapy from March 2017 to October 2021. Exclusion criteria included primary/peritoneal dialysis-related peritonitis, necrotizing pancreatitis, fistulizing inflammatory bowel disease, or upper gastrointestinal tract infection. Patients were assigned into two groups: IV-only or oral step-down therapy. The primary outcome was infection recurrence, defined as re-initiation of antimicrobial agents after a treatment-free period of more than or equal to three days. Secondary outcomes included treatment escalation, repeat source control procedure, treatment-related complications, and all-cause mortality. Results: The cohort consisted of 248 patients (199 IV-only and 49 oral step-down). Patients receiving IV-only therapy had a shorter median antimicrobial duration than the oral step-down group (13 vs. 23 d; p <0.0001). Infection recurrence occurred in 26 (13.1%) and 6 (12.2%) patients in the IV-only and oral step-down groups, respectively (p = 0.88). Treatment escalation, repeat source control, and 28-day mortality were similar between groups. Oral step-down therapy resulted in more adverse drug events (10.2% vs. 3.0%; p = 0.04). Discussion: Transition to oral step-down after initial IV therapy had a similar rate of infection recurrence as IV-only therapy but was associated with a longer duration of antimicrobial therapy and an increased rate of adverse drug reactions. Larger randomized non-inferiority studies are needed to confirm this approach.

Prostaglandin E2 is an unreliable biomarker for inflammation in castrated piglets: a randomized controlled trial assessing pharmaceutical drug efficiency.

OBJECTIVE: To investigate the effect of intranasal (IN) flunixin meglumine (FM) and intra-inguinal (IG) lidocaine on castration inflammation using prostaglandin E2 (PGE2) concentration as a biomarker. METHODS: This randomized controlled trial was conducted in March 2022. Blood was collected at -24, 1, and 24 hours postcastration for PGE2 quantification from 195 piglets that received 1 of 8 treatments: (1) saline (1.5 mL) applied IG and IN (0.2 mL) followed by surgical castration (n = 24); (2) saline (1.5 mL) IG and IN (0.2 mL) followed by sham castration (25); (3) lidocaine (20 mg/kg or 1.5 mL) IG followed by surgical castration (24); (4) lidocaine (20 mg/kg or 1.5 mL) IG followed by sham castration (25); (5) FM (2.2 mg/kg) IN followed by surgical castration (25); (6) FM (2.2 mg/kg) IN followed by sham castration (24); (7) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by surgical castration (24); and (8) lidocaine (20 mg/kg or 1.5 mL) IG and FM (2.2 mg/kg) IN followed by sham castration (24). RESULTS: Prostaglandin E2 concentrations did not increase following the castration procedure and were not an effective biomarker of castration inflammation. Piglets that received lidocaine demonstrated no difference in PGE2 levels across all time points. Piglets administered FM had lower PGE2 concentrations at 1 hour and 20 minutes postdrug administration in both the sham and castrated piglets. CONCLUSIONS: Prostaglandin E2 was not an effective biomarker to quantify castration inflammation. Flunixin meglumine was able to reduce PGE2 concentration in piglets regardless of castration procedure, but lidocaine had no impact. Decreased PGE2 levels in FM-treated pigs are likely associated with the drug's ability to mitigate a noncastration-associated inflammatory process occurring independent of the castration procedure. CLINICAL RELEVANCE: Flunixin meglumine reduced circulating PGE2 concentration in the blood, regardless of the castration procedure, indicating a potential for the drug to mitigate an inflammatory process unrelated to castration.

Development of a Novel Evidence-Based Practice-Specific Competency for Doctor of Physical Therapy Students in Clinical Education: A Modified Delphi Approach.

INTRODUCTION: Evidence-based practice (EBP) results in high-quality care and decreases unwarranted variation in practice. REVIEW OF THE LITERATURE: Few performance criteria related to EBP are included in physical therapy clinical education (CE) performance measures, despite EBP requirements in Doctor of Physical Therapy education. The purpose of this study was to develop EBP-specific competencies that may be used for Doctor of Physical Therapy students for use throughout CE. SUBJECTS: Thirteen subject matter experts (SME) participated in this study. METHODS: Subject matter experts were asked to rank each core EBP competency, from a previously described framework, using a 3-point Likert scale, which included "Not Essential," "Essential," and "Not Sure." A consensus of 70% or greater for the "Essential" rating advanced the competency to the final Delphi round, whereas a consensus of 70% or greater for the "Not Essential" rating was required for competency elimination. Subject matter experts voted to either "Accept" or "Modify" the competencies that had reached the inclusion consensus threshold. All competencies that reached consensus for inclusion after all 3 rounds were included in the final EBP Domain of Competence. RESULTS: Consensus was achieved in round one for 38% (n = 26) of items. In round 2, a consensus was achieved for 20% (n = 8) of items. Of the items remaining after rounds 1 and 2, 6 overarching competencies were identified, and all remaining items served as descriptions and specifications in the final EBP Domain of Competence. DISCUSSION AND CONCLUSIONS: The 6 competencies developed from this study constitute the EBP Domain of Competence and may be used throughout CE to assess students' EBP competency in clinical practice.