Native hepatic T1-time as a non-invasive predictor of diastolic dysfunction and a monitoring tool for disease progression and treatment response in patients with pulmonary hypertension.

AIMS: Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). METHODS AND RESULTS: We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. CONCLUSIONS: Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.

Sarcoma in patients with Lynch syndrome and response to immunotherapy.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant genetic predisposition to multiple malignancies and is characterized by deficient DNA mismatch repair. Increased incidence of sarcomas is not formally ascribed to LS; however, increasing evidence suggests a preponderance of these malignancies in affected families. Sarcomas typically possess a low tumor mutational burden and incite a poor immune infiltrate, thereby rendering them poorly responsive to immunotherapy. METHODS: We searched the University of California, Los Angeles (UCLA) sarcoma program database for patients with a diagnosis of sarcoma and LS from 2016 to 2023. Three such patients were identified and all three were treated with PD1 blockade. RESULTS: We present three cases of LS-associated sarcomas (two soft tissue sarcoma and one osteosarcoma) with increased tumor mutational burdens. These patients were each treated with an anti-PD1 antibody and experienced a response far superior to that reported for non-LS-associated sarcomas. CONCLUSIONS: Increased mutational burden and immune infiltrate are observed for sarcomas associated with LS. Although unselected patients with sarcoma have demonstrated poor response rates to immunotherapy, our findings suggest that patients with Lynch-associated sarcomas are more likely to respond to treatment with anti-PD1. These patients should be given consideration for immunotherapy.

IGF2BP3 as a Prognostic Biomarker in Well-Differentiated/Dedifferentiated Liposarcoma.

BACKGROUND: Although IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking. METHODS: We examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation. RESULTS: Within the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years, p = 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years, p = 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years, p < 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years, p < 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55, p = 0.034). CONCLUSION: IGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival.

Feasibility of periprocedural decision on the administration of intravenous contrast media in MRI for endometriosis.

PURPOSE: To assess the feasibility of a periprocedural decision on the administration of intravenous contrast media in MRI for endometriosis and to evaluate the frequency and reasons of contrast administrations, the corresponding MRI diagnoses, and outcome. METHODS: In this retrospective, descriptive cross-sectional single-center study all patients were included, who received a pelvic MRI for evaluation of endometriosis between April 2021 and February 2023. Frequency and reasons of optional intravenous administration of contrast media, corresponding MRI diagnoses and clinical outcome data were noted after re-review of all images, review of radiology reports and review of patients' medical records. The decision on the administration of intravenous contrast media had been made by experienced radiologists, depending on the findings of the non-contrast sequences and the presence of ancillary questions. RESULTS: 303 consecutive patients (mean age, 33.4 years +/- 8.3 [standard deviation]) were evaluated. Periprocedural decision on the administration of intravenous contrast media had been made in all cases. For 219/303 (72.3%) patients, it was decided after review of the non-contrast sequences and exclusion of ancillary questions that contrast administration was not required. 84/303 (27.7%) patients received contrast media, and the most frequent reasons were indeterminate ovarian lesion (41/84 cases, 48.8%) or suspicion of pelvic venous congestion syndrome (26/84 cases, 31.0%). No relevant differences in patient outcomes could be noted (non-contrast/contrast MRI). CONCLUSIONS: A periprocedural decision on the administration of contrast media in MRI for endometriosis is feasible with little effort. It allows the administration of contrast media to be avoided in most cases. If the administration of contrast media is deemed necessary, repeat examinations can be avoided.

The landscape of drug sensitivity and resistance in sarcoma.

Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, to the point that many rarer subtypes of sarcoma do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity in responses. Overall, novel, personalized approaches for identifying effective treatments are needed to improve patient out-comes. Patient-derived tumor organoids (PDTOs) are clinically relevant models representative of the physiological behavior of tumors across an array of malignancies. Here, we use PDTOs as a tool to better understand the biology of individual tumors and characterize the landscape of drug resistance and sensitivity in sarcoma. We collected n=194 specimens from n=126 sarcoma patients, spanning 24 distinct subtypes. We characterized PDTOs established from over 120 biopsy, resection, and metastasectomy samples. We leveraged our organoid high-throughput drug screening pipeline to test the efficacy of chemotherapeutics, targeted agents, and combination therapies, with results available within a week from tissue collection. Sarcoma PDTOs showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. We found 90 biological pathways that were implicated in response to treatment of bone and soft tissue sarcoma organoids. By comparing functional responses of organoids and genetic features of the tumors, we show how PDTO drug screening can provide an orthogonal set of information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma. In aggregate, we were able to identify at least one effective FDA-approved or NCCN-recommended regimen for 59% of the specimens tested, providing an estimate of the proportion of immediately actionable information identified through our pipeline. Highlights: Standardized organoid culture preserve unique sarcoma histopathological featuresDrug screening on patient-derived sarcoma organoids provides sensitivity information that correlates with clinical features and yields actionable information for treatment guidanceHigh-throughput screenings provide orthogonal information to genetic sequencingSarcoma organoid response to treatment correlates with patient response to therapyLarge scale, functional precision medicine programs for rare cancers are feasible within a single institution.

Behaviors and Advocacy Related to COVID-19 among Cancer Patients: The Health Belief Model and Opportunities for Messaging and Education.

Cancer patients have an increased risk of severe COVID-19 outcomes and were recommended to be vaccinated, wear a mask, practice social distancing, and increase hand hygiene. We used the Health Belief Model (HBM) to identify constructs that were associated with the likelihood of adhering to and advocating for CDC COVID-19 prevention recommendations. We surveyed adult cancer patients who had an onsite appointment at the Penn State Cancer Institute or at the Hematology and Oncology Associates of Northeastern Pennsylvania. Survey measures included adherence to and informing others of COVID-19 recommendations as well as HBM constructs. Relationships between HBM constructs and outcomes were assessed with Spearman's correlation and multivariable ordinal logistic regression. Of the 106 participants who completed the survey for our objectives of interest, 76% always wore a mask, 29% always practiced social distancing, and 24% washed their hands at least 10 times a day. Limited advocacy behaviors were captured for the COVID-19 vaccine (30%), social distancing (36%), and wearing masks (27%). Perceived benefits, perceived barriers, and cues-to-action were positively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients, whereas perceived susceptibility and self-efficacy were negatively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients. Perceived benefits may be the strongest predictor for adherence and advocacy for specific COVID-19 guidelines. Future messaging and educational campaigns focused on improving adherence to or advocacy of specific health behaviors should be informed by the HBM and originate from multiple outlets.

[Acute mesenteric ischemia-An overview and recommendations (S2k analogous) of the World Society of Emergency Surgery]. / Die akute Mesenterialischämie ­ eine Übersicht und Empfehlungen (S2k-analog) der World Society of Emergency Surgery.

Acute mesenteric ischemia is a severe illness, which if untreated, rapidly leads to a critical condition with sepsis, multiple organ failure and death in affected patients. The diagnosis and initiation of treatment of acute mesenteric ischemia should be performed as early and expeditiously as possible and follows the principle of the shortest possible time to reperfusion. Otherwise, the outcome of the patient rapidly deteriorates. The treatment algorithm should be adapted to the pathogenesis of the ischemia, the clinical condition and symptoms of the patients. With clinical signs of peritonitis, intestinal gangrene must be assumed and the abdomen should be surgically explored to detect and treat possible foci of sepsis at an early stage. The treatment of acute mesenteric ischemia should always be performed by an interdisciplinary team with all surgical and interventional options for intestinal revascularization as well as comprehensive intensive care medicine according to the standards of the Intestinal Stroke Center described in the literature. A short duration to revascularization and treatment in this interdisciplinary concept improves the outcome of patients with acute mesenteric ischemia. The World Society of Emergency Surgery provides expert consensus-based recommendations for the diagnosis and treatment of acute mesenteric ischemia; however, there is still a significant lack of broad high-quality evidence for this critical illness. Recommendations of the German specialist societies are urgently needed to ensure appropriate care, from the initial diagnostics to treatment and aftercare, for patients with suspected mesenteric ischemia in this country.

Fibroblast Activation Protein Expression in Sarcomas.

Objectives: Fibroblast activation protein alpha (FAP) is highly expressed by cancer-associated fibroblasts in multiple epithelial cancers. The aim of this study was to characterize FAP expression in sarcomas to explore its potential utility as a diagnostic and therapeutic target and prognostic biomarker in sarcomas. Methods: Available tissue samples from patients with bone or soft tissue tumors were identified at the University of California, Los Angeles. FAP expression was evaluated via immunohistochemistry (IHC) in tumor samples (n = 63), adjacent normal tissues (n = 30), and positive controls (n = 2) using semiquantitative systems for intensity (0 = negative; 1 = weak; 2 = moderate; and 3 = strong) and density (none, <25%, 25-75%; >75%) in stromal and tumor/nonstromal cells and using a qualitative overall score (not detected, low, medium, and high). Additionally, RNA sequencing data in publicly available databases were utilized to compare FAP expression in samples (n = 10,626) from various cancer types and evaluate the association between FAP expression and overall survival (OS) in sarcoma (n = 168). Results: The majority of tumor samples had FAP IHC intensity scores ≥2 and density scores ≥25% for stromal cells (77.7%) and tumor cells (50.7%). All desmoid fibromatosis, myxofibrosarcoma, solitary fibrous tumor, and undifferentiated pleomorphic sarcoma samples had medium or high FAP overall scores. Sarcomas were among cancer types with the highest mean FAP expression by RNA sequencing. There was no significant difference in OS in patients with sarcoma with low versus high FAP expression. Conclusion: The majority of the sarcoma samples showed FAP expression by both stromal and tumor/nonstromal cells. Further investigation of FAP as a potential diagnostic and therapeutic target in sarcomas is warranted.

FAPI PET Signal in Hibernoma Reflects FAP Expression in Tumor Vasculature Cells.

ABSTRACT: A 43-year-old man with a growing mass in the right groin, concerned for liposarcoma, underwent MRI and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46 PET/CT before surgery. Fibroblast activation protein inhibitor PET/CT demonstrated increased uptake (SUV max , 3.2) predominantly in the solid portion, where MRI showed gadolinium enhancement. The patient subsequently underwent surgery and was diagnosed with hibernoma. The immunohistochemistry of the tumor revealed the fibroblast activation protein expression in the fibrovascular network and myofibroblastic cells of the tumor. This case suggests that the FAPI uptake can be affected by the vascular cells, and thus, a careful interpretation of the FAPI PET signal may be needed.

Deep Infiltrating Endometriosis: Diagnostic Accuracy of Preoperative Magnetic Resonance Imaging with Respect to Morphological Criteria.

Several current guidelines recommend imaging in the diagnostic work-up of deep infiltrating endometriosis (DIE). The purpose of this retrospective diagnostic test study was to evaluate the diagnostic accuracy of MRI compared to laparoscopy for the identification of pelvic DIE, considering lesion morphology using MRI. In all, 160 consecutive patients were included who received pelvic MRI for evaluation of endometriosis between October 2018 and December 2020 and underwent subsequent laparoscopy within 12 months of the MRI examination. MRI findings were categorized for suspected DIE using the Enzian classification and were additionally graded using a newly suggested deep infiltrating endometriosis morphology score (DEMS). Endometriosis was diagnosed in 108 patients (all types, i.e., purely superficial and DIE), of which 88 cases were diagnosed with DIE and 20 with solely superficial peritoneal endometriosis (i.e., not deep infiltrating endometriosis/DIE). The overall positive and negative predictive values of MRI for the diagnosis of DIE, including lesions with assumed low and medium certainty of DIE on MRI (DEMS 1-3), were 84.3% (95% CI: 75.3-90.4) and 67.8% (95% CI: 60.6-74.2), respectively, and 100.0% and 59.0% (95% CI: 54.6-63.3) when strict MRI diagnostic criteria were applied (DEMS 3). Overall sensitivity of MRI was 67.0% (95% CI: 56.2-76.7), specificity was 84.7% (95% CI: 74.3-92.1), accuracy was 75.0% (95% CI: 67.6-81.5), positive likelihood ratio (LR+) was 4.39 (95% CI: 2.50-7.71), negative likelihood ratio (LR-) was 0.39 (95% CI: 0.28-0.53), and Cohen's kappa was 0.51 (95% CI: 0.38-0.64). When strict reporting criteria are applied, MRI can serve as a method to confirm clinically suspected DIE.

Nutrient dynamics of 12 Sphagnum species during establishment on a rewetted bog.

Peatland degradation through drainage and peat extraction have detrimental environmental and societal consequences. Rewetting is an option to restore lost ecosystem functions, such as carbon storage, biodiversity and nutrient sequestration. Peat mosses (Sphagnum) are the most important peat-forming species in bogs. Most Sphagnum species occur in nutrient-poor habitats; however, high growth rates have been reported in artificial nutrient-rich conditions with optimal water supply. Here, we demonstrate the differences in nutrient dynamics of 12 Sphagnum species during their establishment in a 1-year field experiment at a Sphagnum paludiculture area in Germany. The 12 species are categorized into three groups (slower-, medium- and fast-growing). Establishment of peat mosses is facilitated by constant supply of nutrient-rich, low pH, and low alkalinity surface water. Our study shows that slower-growing species (S. papillosum, S. magellancium, S. fuscum, S. rubellum, S. austinii; often forming hummocks) displayed signs of nutrient imbalance. These species accumulated higher amounts of N, P, K and Ca in their capitula, and had an elevated stem N:K quotient (>3). Additionally, this group sequestered less C and K per m2 than the fast and medium-growing species (S. denticulatum, S. fallax, S. riparium, S. fimbriatum, S. squarrosum, S. palustre, S. centrale). Lower lawn thickness may have amplified negative effects of flooding in the slower-growing species. We conclude that nutrient dynamics and carbon/nutrient sequestration rates are species-specific. For bog restoration, generating ecosystem services or choosing suitable donor material for Sphagnum paludiculture, it is crucial to consider their compatibility with prevailing environmental conditions.

Does "Low-Grade" Dedifferentiated Liposarcoma Exist? The Role of Mitotic Index in Separating Dedifferentiated Liposarcoma From Cellular Well-differentiated Liposarcoma.

BACKGROUND: Subjective, varying criteria identify "low-grade" dedifferentiation in well-differentiated/dedifferentiated liposarcoma (WD/DDLPS). The value of mitotic rate (MR) in defining DDLPS is not confirmed. We studied all patients with the resection of their primary or first recurrence retroperitoneal WD/DDLPS at our institution to determine the value of MR in diagnosing DDLPS and if MR associates with patient survival. DESIGN: Ninety-eight patients with retroperitoneal WD/DDLPS operated at our institution from January 1, 1989 to December 31, 2013 were included. Cases were defined as acellular (AC) WDLPS, LS0-4 (tumors with non-lipogenic areas and MR 0-4/10HPFs) or LS5+(non-lipogenic areas, MR≥5/10 HPFs) and graded using the French system. Kaplan-Meier survival estimates with log-rank test and multivariate Cox (mCox) analyses were performed. RESULTS: Follow-up was available on all patients (median 9.3 y, range 0.02-23.16 y). Kaplan-Meier demonstrated a significant ( P =0.004) difference in disease-specific survival (DSS) among the 3 groups. mCox demonstrated no difference in DSS between the AC and LS0-4 groups (HR 1.51; 95% CI 0.57-3.99, P =0.412) but significantly lower DSS in the LS5+group compared with the AC group (HR 2.68; 95% CI 1.07-6.71, P =0.035). The difference in DSS was not significant between grade 2 and 3 tumors ( P =0.094). DSS between MR 5-19/10 HPFs and MR20+/10 HPFs subgroups was significant ( P =0.007) but by mCox did not reach significance (HR 2.47; 95% CI 0.96-6.35, P =0.060). CONCLUSION: This study confirms that MR distinguishes DDLPS from WDLPS with non-lipogenic areas, also known as cellular WDLPS. For consistency in diagnosis and research, only WD/DDLPS with≥5 mitoses/10 HPFs should be considered DDLPS.

Value of Right and Left Ventricular T1 and T2 Blood Pool Mapping in Patients with Chronic Thromboembolic Hypertension before and after Balloon Pulmonary Angioplasty.

BACKGROUND: Parametric imaging has taken a steep rise in recent years and non-cardiac applications are of increasing interest. Therefore, the aim of our study was to assess right (RV) and left ventricular (LV) blood pool T1 and T2 values in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to control subjects and their correlation to pulmonary hemodynamic. METHODS: 26 patients with CTEPH (mean age 64.8 years ± 12.8 SD; 15 female), who underwent CMR and right heart catheterization (RHC) before and 6-months after balloon pulmonary angioplasty (BPA), were retrospectively included. Ventricular blood pool values were measured, compared to control subjects (mean age 40.5 years ± 12.8 SD; 16 female) and correlated to invasive measures (CI, mPAP, PVR). RESULTS: In both, control subjects and CTEPH patients, RVT1 and RVT2 were significantly reduced compared to LVT1 and LVT2. Compared to control subjects, RVT2 was significantly reduced in CTEPH patients (p = 0.0065) and increased significantly after BPA (p = 0.0048). Moreover, RVT2 was positively correlated with CI and negatively correlated with mPAP and PVR before (r = 0.5155, r = -0.2541, r = -0.4571) and after BPA (r = 0.4769, r = -0.2585, r = -0.4396). CONCLUSION: Ventricular blood pool T2 mapping might be novel non-invasive CMR imaging marker for assessment of disease severity, prognosis, follow-up and even therapy monitoring in PH.

Human papillomavirus related oropharyngeal cancer: identifying and quantifying topics of patient interest.

OBJECTIVE: As the incidence of human papillomavirus related oropharyngeal cancer continues to rise, it is increasingly important for public understanding to keep pace. This study aimed to identify areas of patient interest and concern regarding human papillomavirus and oropharyngeal cancer. METHOD: This study was a retrospective survey of search queries containing the keywords 'HPV cancer' between September 2015 and March 2021. RESULTS: There was 3.5-fold more interest in human papillomavirus related oropharyngeal cancer (15 800 searches per month) compared with human papillomavirus related cervical cancer (4500 searches per month). Among searches referencing cancer appearance, 96.8 per cent pertained to the head and neck region (3050 searches per month). Among vaccination searches, 16 of 47 (34.0 per cent; 600 searches per month) referenced human papillomavirus vaccines as being a cause of cancer rather than preventing cancer. CONCLUSION: The vast majority of online searches into human papillomavirus cancer pertain to the oropharynx. There are relatively few search queries on the topic of vaccination preventing human papillomavirus associated oropharyngeal cancer, which highlights the continued importance of patient education and awareness campaigns.

Lifelong Imaging Surveillance is Indicated for Patients with Primary Retroperitoneal Liposarcoma.

BACKGROUND: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) after surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined because the natural history of RP-LPS after treatment is poorly understood. This study evaluated the long-term risk of recurrence and disease-specific survival (DSS) for a cohort of patients with at least 10 years of progression-free survival (10yr-PFS) from their primary resection. METHODS: The prospective University of California, Los Angeles (UCLA) Sarcoma Database identified RP-LPS patients with 10yr-PFS after initial resection. The patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. The time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. RESULTS: From 1972 to 2010, 76 patients with RP-LPS had at least 10 years of follow-up evaluation. Of these 76 patients, 39 (51%) demonstrated 10yr-PFS. The median follow-up period was 15 years (range 10-33 years). Among the 10yr-PFS patients, 49% (19/39) experienced a recurrence at least 10 years after surgery. Of those who experienced recurrence, 42% (8/19) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or perioperative treatment with radiation or chemotherapy. CONCLUSION: Patients who have primary RP-LPS treated with surgical resection ± multimodality therapy face a long-term risk of recurrence and disease-specific death unacknowledged by current surveillance imaging guidelines. Among the patients with 10yr-PFS, 49% experienced a recurrence, and 42% of those died of disease. These findings suggest a need for lifelong surveillance imaging for patients with RP-LPS.

Exercise MR-proANP unmasks latent right heart failure in CTEPH.

OBJECTIVE: The present study was designed to investigate the dynamics of right atrial pressure (RAP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) during physical exercise in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. METHODS: This prospective observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure. RESULTS: During eRHC mean RAP increased from 6 mmHg (standard deviation, SD 4) to 16 mmHg (SD 7; p < 0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs = 0.61; p < 0.001) and at peak exercise (rs = 0.66; p < 0.001). Logistic regression analysis revealed the peak MR-proANP level (B = 0.058; p = 0.004) and the right atrial area (B = 0.389; p < 0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC = 0.81) and recovery level ≥159 pmol/L (AUC = 0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked right heart failure in 39% of patients with normal RAP at rest; these patients were also characterized by a more distinct increase in MR-proANP levels (p = 0.005) and higher peak (p < 0.001) and recovery levels (p < 0.001). CONCLUSIONS: RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients.

[Growth trajectories of intrinsic value beliefs in mathematics and French: Relations with career orientations]. / Wachstumsverläufe der intrinsischen Wertüberzeugungen in Mathematik und Französisch: Zusammenhänge mit Berufsorientierungen.

This longitudinal study investigated different trajectories in the development of intrinsic value beliefs in the subjects Mathematics and French in Grades 9 to 11 and their correlations with career aspirations. Using data from 850 students from German-Swiss high schools (54% female, age T1: 15.6 years), five distinct growth classes were identified in a bivariate growth model. Two of these classes showed clear differentiation between intrinsic value beliefs regarding the two subjects and stable growth in the preferred subject. The other three classes were characterized by mean differences (high, medium, low intrinsic value beliefs) and moderate decline in both subjects. The five growth classes were associated with different career orientations at the end of the 11th grade, with students exhibiting particularly high career orientations in one subject when intrinsic value regarding the other subject was low. Gender differences in career orientations could be fully explained by gender membership in the five growth classes.

Sphagnum bleaching: Bicarbonate 'toxicity' and tolerance for seven Sphagnum species.

Growth and functioning of Sphagnum mosses are closely linked to water level and chemistry. Sphagnum mosses occur in wet, generally acidic conditions, and when buffered, alkaline water is known to negatively impact Sphagnum. The effects of time, dose and species-specific responses of buffered, alkaline water on Sphagnum are largely unknown. We investigated the effects of bicarbonate and calcium on the survival, growth and physiological functioning of seven Sphagnum species occurring in contrasting environments, from raised bogs to (rich) fens. Mosses were submerged in different concentrations of bicarbonate and calcium solutions for 10 weeks under climate-controlled circumstances. After 2 weeks, all species exposed to the high bicarbonate treatment (2.0 mM) showed severe potassium leakage and swift discoloration. In contrast, species showed differential responses to the intermediate bicarbonate treatment (0.8 mM), some with a later onset of potassium leakage. S. squarrosum, S. teres & S. contortum generally persisted the longest, with all species dying after 6 to 10 weeks. Calcium alone, in contrast, negatively affected S. squarrosum, S. teres & S. contortum, causing discoloration and potassium leakage. Our study shows enrichment with bicarbonate, but not calcium, is detrimental for most Sphagnum species tested. A mechanistic model was developed that is consistent with dose and duration dependence and the species specificity. Future conservation and restoration measures for Sphagnum-dominated habitats and Sphagnum farming (cultivation, production and harvest of Sphagnum moss biomass) should limit flooding with bicarbonate-rich waters while investigating new management options, like acidifying surface waters to lower bicarbonate levels.