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In recent decades, the scientific community has seen an increased interest in rigor and reproducibility. In 2017, concerns about methodological thoroughness and reporting practices were implicated as significant barriers to reproducibility within the preclinical cardiovascular literature, particularly in studies using animal research. The Langendorff, whole heart technique has proven to be an invaluable research tool, being modified in a myriad of ways to probe questions across the spectrum of physiological and pathophysiological functions of the heart. As a result, significant variability in the application of the Langendorff technique exists. This literature review quantifies the different methods employed in the implementation of the Langendorff technique and provides brief examples of how individual parametric differences can impact the outcomes and interpretation of studies. From 2017 to 2020, significant variability of animal models, anesthesia, cannulation time, perfusate composition, pH, and temperature demonstrate that the technique has diversified to meet new challenges and answer different scientific questions. The review also reveals which individual methods are most frequently reported, even if there is no explicit agreement upon which parameters should be reported. The analysis of methods related to the Langendorff technique suggests a framework for considering methodological approach when interpreting seemingly contradictory results, rather than concluding that results are irreproducible. [ABSTRACT FROM AUTHOR]

Purpose: The study purpose was to capture the clinical practice patterns of speech-language pathologists (SLPs) treating mild traumatic brain injury (mTBI; concussion). Study aims were to (a) characterize expert SLP practice patterns for the management of mTBI and (b) use qualitative content analysis to explore areas of quantitative variability within participants' responses. Method: Using a modified Delphi approach, SLPs completed an online survey, with Round 1 responses shaping questions for Round 2. Round 2 results were analyzed using a concurrent partially mixed-methods approach with quantitative and qualitative items. Quantitative consensus agreement levels were set prestudy at 75% agreement or higher. Topic-level items that did not reach consensus were analyzed using qualitative content analysis. Participants: SLPs engaging in a specialty mTBI-SLP networking group were invited to participate. Round 1 had nine participants (United States: 4, Canada: 5). Round 2 had 18 participants (United States: 12, Canada: 6), with a mean of 15.7 years of experience in mTBI (range: 3-33) and a mean of 7.6 clients with mTBI seen weekly (range: 1-25). Results: Nearly all topic-level practice items met quantitative consensus (42/45). Consensus areas included using conceptual frameworks, interprofessional teaming, assessment and intervention practices, goal setting, and outcomes. Functional, collaborative, and client-centered care anchored clinical practice. Areas lacking consensus included SLP roles in mTBI mental and somatic health symptoms, specific measurement tools, and intervention dosages. Qualitative themes that emerged included limited interprofessional awareness for the role of SLPs in mTBI and challenges in measurement selection. Conclusions: Study aims were met with clear consensus on clinical patterns implemented by SLPs specializing in mTBI. Results will inform both current clinical practices and future practice guidelines. High-level guidance and advocacy are needed to clarify SLP practice concerns and advance interprofessional education. Future work should address identified gaps, including targeted assessment tools and consensus on intervention methods. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate changes in cognitive-communication performance using Woodcock-Johnson IV Tests (WJIV) from pre-injury baseline to post sportrelated concussion. It was hypothesized that individual subtest performances would decrease postinjury in symptomatic individuals. Method: This prospective longitudinal observational nested cohort study of collegiate athletes assessed cognitivecommunicative performance at preseason baseline and postinjury. Three hundred and forty-two male and female undergraduates at high risk for sport-related concussion participated in preseason assessments, and 18 individuals met criteria post injury. WJIV subtest domains included Word Finding, Speeded Reading Comprehension, Auditory Comprehension, Verbal Working Memory, Story Retell, and Visual Processing (letter and number). The power calculation was not met, and therefore data were conservatively analyzed with descriptive statistics and a planned subgroup analysis based on symptomatology. Results: Individual changes from baseline to postinjury were evaluated using differences in standard score performance. For symptomatic individuals, mean negative decreases in performance were found for Retrieval Fluency, Sentence Reading Fluency, Pattern Matchings, and all cluster scores postinjury. Individual performance declines also included decreases in story retell, verbal working memory, and visual processing. Conclusions: This study identified within-subject WJIV performance decline in communication domains post sport-related concussion and reinforces that cognitivecommunication dysfunction should be considered in mild traumatic brain injury. Key cognitive-communication areas included speeded naming, reading, and verbal memory, though oral comprehension was not sensitive to change. Future clinical research across diverse populations is needed to expand these preliminary findings. [ABSTRACT FROM AUTHOR]

Objective: Social deficits are already exhibited by people at risk for schizophrenia‐spectrum disorders. Technological advances have made passive detection of social deficits possible at granular levels. Method: In this real‐world study, we tested if schizotypy status (high/low) predicted two types of social behavior: (1) being around other people; and (2) actively socializing with others. We also examined if schizotypy influences relationships between social behavior and affect using subjective and objective instruments. Results: Our findings revealed that socializing with others was significantly decreased in the high schizotypy group. Positive affect increased in social situations and predicted later social behavior in those low, but not high, in schizotypy. Conclusion: Decreased social behavior in schizotypy may be explained, in part, by these individuals being less incentivized than their peers to pursue social situations. Future studies should test this explanation in larger samples exhibiting elevated positive, negative, and disorganized schizotypy traits. [ABSTRACT FROM AUTHOR]

Parents, teachers, and paraeducators at three inclusive schools were interviewed as part of a qualitative study to investigate perceptions regarding a quality educational program for students with moderate-severe disabilities. Instead of looking at schools engaged in a systematic change process from separate to inclusive education for students with severe disabilities, a major premise of this study was that all students, regardless of ability or disability, were educated together in chronologically age appropriate general education classrooms (preschool through 8th grade). The intent of this study was to determine what key stakeholders (parents, teachers, and paraeducators) felt was a good educational program for students with moderate-severe disabilities after an inclusive placement was a given. Fifty-eight participants were interviewed (18 parents, 23 teachers, and 17 paraeducators) representing four preschool children, nine elementary students, and five middle school students all having moderate-severe and multiple disabilities. A constant comparison methodology was used to analyze the data across both age of target child and role of stakeholder. Findings revealed 12 themes that highlighted the benefits of inclusive education for all students, specific components that needed to be in place to ensure a quality education, and typical goals for the future. Implications for the field were discussed. [ABSTRACT FROM AUTHOR]

Describes the design and use of daily schedules for students with moderate or severe disabilities, highlighting the multiple learning opportunities provided. Advantages of schedule use; Types of daily schedules; Considerations for developing schedules. INSET: Interviews with teachers..

Disorganized speech is a key component of formal thought disorder (FTD) in schizophrenia. Recent work has tied disorganized speech to deficits in metacognition, or one's ability to integrate experiences to form complex mental representations. The level of FTD at which differences in metacognitive capacity emerge remains unclear. Across two studies, using different cut scores to form FTD groups, we aimed to 1) explore the relationship between disorganized speech and metacognition and 2) compare trained rater and automated analysis methods. Clinical interviews were coded for disorganized speech and metacognition using the Communication Disturbances Index (CDI), Coh-Metrix multidimensional indices, and Metacognition Assessment Scale. In Study 1, we examined CDI and Coh-Metrix's ability to predict metacognition in FTD (n = 16) and non-FTD (n = 29) groups. We hypothesized the FTD group would have lower metacognition and that both CDI and Coh-Metrix would account for significant variance in metacognition. In Study 2, we conducted the same analyses with an independent sample using more stringent FTD cut scores (FTD: n = 23; non-FTD: n = 23). Analyses indicated that at a moderate but not mild cutoff: 1) automated methods differentiated FTD and non-FTD groups, 2) differences in metacognition emerged, and 3) behavioral measures accounted for significant variance (34%) in metacognition. Results emphasize the importance of setting the FTD cutoff at a moderate level and using samples that contain high levels of FTD. Findings extend research linking FTD and metacognition and demonstrate the benefit of pairing trained rater and automated speech measures. • Automated analytical tools are novel methods to assess speech in schizophrenia. • Group differences emerged at a moderate formal thought disorder threshold. • Findings suggest using a moderate rather than mild threshold for thought disorder. • Patients with moderate thought disorder had lower metacognition. • Together, speech measures predicted metacognition in people with schizophrenia. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary edema with low systemic oxygen (O2) levels is a hallmark of acute decompensated heart failure (HF) related to elevated left heart filling pressures. However, less is known about arterial O2 (PaO2) responses during exercise in patients with heart failure with preserved ejection fraction (HFpEF). Hypothesis: We hypothesized that changes in PaO2 in response to exercise are governed by extra-cardiac organ systems rather than the degree of elevation in pulmonary capillary wedge pressure (PCWP). Methods: We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring in 411 patients (age 58±2.9, 61% female, BMI 29.7±0.7, LVEF 66±2.6 %; mean±SEM) with HFpEF defined by ACC/AHA criteria with exclusion of patients with O2-dependent lung disease. Results: Exercise PaO2 was associated with peak VO2 (r=0.22, p<0.001) but average PaO2 increased only modestly from rest to peak exercise (3.1±0.7mmHg) and overt O2 desaturation was uncommon (1.5% of patients had PaO2<55mmHg and O2sat ≤ 88%). Exercise change in PaO2 was not associated with resting PCWP (r=0.05, p=0.27) or exercise PCWP (r<0.01, P=0.7) (Figure). Change in PaO2was correlated with % predicted diffusion capacity of the lungs (DLCO) (r=0.28, p<0.001) despite relatively normal average spirometry values (FVC 93±1, FEV1 89±5, FVC/FEV 96±5, % predicted mean±SEM). Pulmonary artery pressure (PAP) and transpulmonary pressure gradient (TPG) were also associated with change in PaO2 (r=-0.18 (PAP), r=-0.25 (TPG), p<0.001) in multivariable models adjusting for age, sex, and BMI. Conclusions: Pulmonary and pulmonary vascular function, but not left sided filling pressures, relate to changes in PaO2 during incremental exercise in HFpEF. These findings highlight the important role of extra-cardiac organ systems, specifically the lungs, in mediating systemic O2 bioavailability during exercise in HFpEF. [ABSTRACT FROM AUTHOR]

Diminished productivity and elevated disorganization have been detected in the speech of individuals with schizotypy. However, the underlying mechanisms for these disruptions are not well understood. Separate lines of research suggest potential contributions from cognitive and affective systems. In this study, disorganized speech and speech production were examined in speech samples generated by schizotypy (n = 47) and non-schizotypy (n = 51) groups by assessing "reactivity" (i.e., a change in experimental compared with baseline conditions) across baseline, affective, and dual-task (i.e., cognitive) conditions. Relationships with social functioning were also examined within each group. Three key findings emerged: 1) compared to the non-schizotypy group, those with schizotypy exhibited diminished speech production in the affective condition and affective reactivity was observed; 2) the schizotypy group displayed greater levels of disorganized speech in dual-task conditions and cognitive reactivity was observed; and 3) affective reactivity for disorganized speech was linked to worse social functioning within the schizotypy group. This study provides evidence that cognitive and affective systems are uniquely involved in separate characteristics of speech in schizotypy. At this stage, cognitive systems appear to have a specific role in the organization of speech, whereas affective systems are more heavily involved in speech production. Regarding the association between affective reactivity and social functioning, previous research has demonstrated individuals highly reactive to emotional stimuli carry additional risk for conversion to psychosis. Future research identifying a subset with schizotypy who demonstrate affective reactivity could lead to a better understanding of links between schizotypy and future psychosis symptoms. [ABSTRACT FROM AUTHOR]

Background: Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear.Objectives: This study sought to investigate the association of exPH with clinical determinants and outcomes.Methods: The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality.Results: Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n = 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p = 0.003). Both pre- and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both).Conclusions: Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF. Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes. Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met Heart Failure Society of America (HFSA) criteria for HFpEF. Clinical profiles and exercise capacity varied across definitions, with peak oxygen uptake of 16.2±5.2 (ACC/AHA), 14.1±4.2 (ESC), and 12.7±3.1 mL·kg-1·min-1 (HFSA). A total of 243 patients had hemodynamic evidence of HFpEF (abnormal rest or exercise filling pressures), of whom 222 met ACC/AHA, 161 met ESC, and 41 met HFSA criteria. Over a mean follow-up of 3.8 years, the incidence of cardiovascular outcomes ranged from 75 (ACC/AHA) to 298 events per 1000 person-years (HFSA). Application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication. Conclusions: Use of different HFpEF classifications variably enriches for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure highlights the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF subgrouping to test therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Hepcidin is a master regulator of iron homeostasis that reduces iron absorption when circulating levels are elevated. In preclinical models, iron deficiency and inappropriately elevated hepcidin levels have been implicated in pulmonary arterial hypertension. However, the role of hepcidin dysregulation on pulmonary vascular function in patients with dyspnea on exertion (DOE) and preserved ejection fraction remains unclear. Hypothesis: We hypothesized that a low ratio of transferrin saturation to hepcidin is associated with abnormal pulmonary vascular responses during exercise. Methods: Cardiopulmonary exercise testing (CPET) using cycle ergometry with invasive hemodynamic monitoring was performed in 127 patients with preserved ejection fraction (LVEF ≥ 50%) undergoing evaluation for dyspnea. Serum hepcidin and transferrin saturation (Tsat) were measured at the time of CPET and the ratio (Tsat/Hepcidin) was used as a measure of iron homeostasis and hepcidin dysregulation, with low values reflecting inappropriate elevation in hepcidin level relative to iron bioavailability. Results: Patients had the following characteristics (mean ± SEM): age 58 ± 1; 28% male; BMI 29.6 ± 0.6 kg/m2; Hb 12.0 ± 0.1 g/dL, Tsat 24.8 ± 1.0%; hepcidin 17.9 ± 1.4 ng/ml; Tsat/Hepcidin 2.7 ± 0.2 ml/ng. The Tsat/Hepcidin ratio inversely correlated with pulmonary vascular resistance (PVR) at rest (r = -0.25, p=0.005) and peak exercise (r = -0.27, p=0.002, A-B). Lower Tsat/Hepcidin ratio was also associated with lower peak VO2, lower cardiac index, higher PA pressures, and higher PAP / CO slope (C), but did not associate with exercise pulmonary arterial wedge pressure (PAWP; r = -0.13, p = 0.13). Conclusion: Hepcidin dysregulation, reflected by low Tsat/Hepcidin ratio, is more closely related to pulmonary vascular dysfunction than left ventricular dysfunction during exercise in patients being evaluated for dyspnea on exertion. [ABSTRACT FROM AUTHOR]

Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF.Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes.Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met Heart Failure Society of America (HFSA) criteria for HFpEF. Clinical profiles and exercise capacity varied across definitions, with peak oxygen uptake of 16.2±5.2 (ACC/AHA), 14.1±4.2 (ESC), and 12.7±3.1 mL·kg-1·min-1 (HFSA). A total of 243 patients had hemodynamic evidence of HFpEF (abnormal rest or exercise filling pressures), of whom 222 met ACC/AHA, 161 met ESC, and 41 met HFSA criteria. Over a mean follow-up of 3.8 years, the incidence of cardiovascular outcomes ranged from 75 (ACC/AHA) to 298 events per 1000 person-years (HFSA). Application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication.Conclusions: Use of different HFpEF classifications variably enriches for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure highlights the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF subgrouping to test therapeutic interventions. [ABSTRACT FROM AUTHOR]