Tailoring the Photophysical Properties of a Homoleptic Iron(II) Tetra N-Heterocyclic Carbene Complex by Attaching an Imidazolium Group to the (C∧N∧C) Pincer Ligand─A Comparative Study.

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilization of the metal-to-ligand charge transfer (MLCT) state and destabilization of the metal-centered (MC) states. This resulted in an improved excited-state lifetime of 16 ps compared to the 9 ps for the unsubstituted parent compound [Fe(pbmi)2](PF6)2 (pbmi = (pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) as well as a stronger MLCT absorption band extending more toward the red spectral region. However, compared to the carboxylic acid derivative [Fe(cpbmi)2](PF6)2 (cpbmi = 1,1'-(4-carboxypyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)), the excited-state lifetime of [Fe(miHpbmi)2](PF6)4 is the same, but both the extinction and the red shift are more pronounced for the former. Hence, this makes [Fe(miHpbmi)2](PF6)4 a promising pH-insensitive analogue of [Fe(cpbmi)2](PF6)2. Finally, the excited-state dynamics of the title compound [Fe(miHpbmi)2](PF6)4 was investigated in solvents with different viscosities, however, showing very little dependency of the depopulation of the excited states on the properties of the solvent used.

Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.

BACKGROUND: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP. METHODS: We analyzed all 8 CELA3B exons in 550 German non-alcoholic CP (NACP) patients and in 241 German controls by targeted DNA sequencing. In addition, we analyzed exons 6 and 7 by Sanger sequencing and the c.129+1G>A variant by melting curve analysis in 1078 further German controls. As replication cohort, we investigated up to 243 non-German European NACP patients and up to 1665 controls originating from Poland, Hungary, and Sweden. We assessed the cellular secretion and the elastase activity of recombinant CELA3B variants. RESULTS: In the German discovery cohort, we detected a splice-site variant in intron 2, c.129+1G>A, in 9/550 (1.64%) CP patients and in 5/1319 (0.38%) controls (P=0.007, OR=4.4, 95% CI=1.5-13.0). In the European replication cohort, this variant was also enriched in patients (9/178 [5.06%]) versus controls (13/1247 [1.04%]) (P=0.001, OR=5.1, 95% CI=2.1-12.0). We did not find the two previously reported codon 90 variants, p.R90C and p.R90L. CONCLUSIONS: Our data indicate that CELA3B is a susceptibility gene for CP. In contrast to previous reports suggesting that increased CELA3B activity is associated with CP risk, the splice-site variant identified here is predicted to cause diminished CELA3B expression. How reduced CELA3B function predisposes to pancreatitis remains to be elucidated.

Variants in the pancreatic CUB and zona pellucida-like domains 1 (CUZD1) gene in early-onset chronic pancreatitis - A possible new susceptibility gene.

OBJECTIVE: Non-alcoholic chronic pancreatitis (NACP) frequently develops in the setting of genetic susceptibility associated with alterations in genes that are highly expressed in the pancreas. However, the genetic basis of NACP remains unresolved in a significant number of patients warranting a search for further risk genes. DESIGN: We analyzed CUZD1, which encodes the CUB and zona pellucida-like domains 1 protein that is found in high levels in pancreatic acinar cells. We sequenced the coding region in 1163 European patients and 2018 European controls. In addition, we analyzed 297 patients and 1070 controls from Japan. We analyzed secretion of wild-type and mutant CUZD1 from transfected cells using Western blotting. RESULTS: In the European cohort, we detected 30 non-synonymous variants. Using different prediction tools (SIFT, CADD, PROVEAN, PredictSNP) or the combination of these tools, we found accumulation of predicted deleterious variants in patients (p-value range 0.002-0.013; OR range 3.1-5.2). No association was found in the Japanese cohort, in which 13 non-synonymous variants were detected. Functional studies revealed >50% reduced secretion of 7 variants, however, these variants were not significantly enriched in European CP patients. CONCLUSION: Our data indicate that CUZD1 might be a novel susceptibility gene for NACP. How these variants predispose to pancreatitis remains to be elucidated.

HIPPIE: a new platform for ambient-pressure X-ray photoelectron spectroscopy at the MAX IV Laboratory.

HIPPIE is a soft X-ray beamline on the 3 GeV electron storage ring of the MAX IV Laboratory, equipped with a novel ambient-pressure X-ray photoelectron spectroscopy (APXPS) instrument. The endstation is dedicated to performing in situ and operando X-ray photoelectron spectroscopy experiments in the presence of a controlled gaseous atmosphere at pressures up to 30 mbar [1 mbar = 100 Pa] as well as under ultra-high-vacuum conditions. The photon energy range is 250 to 2200 eV in planar polarization and with photon fluxes >1012 photons s-1 (500 mA ring current) at a resolving power of greater than 10000 and up to a maximum of 32000. The endstation currently provides two sample environments: a catalysis cell and an electrochemical/liquid cell. The former allows APXPS measurements of solid samples in the presence of a gaseous atmosphere (with a mixture of up to eight gases and a vapour of a liquid) and simultaneous analysis of the inlet/outlet gas composition by online mass spectrometry. The latter is a more versatile setup primarily designed for APXPS at the solid-liquid (dip-and-pull setup) or liquid-gas (liquid microjet) interfaces under full electrochemical control, and it can also be used as an open port for ad hoc-designed non-standard APXPS experiments with different sample environments. The catalysis cell can be further equipped with an IR reflection-absorption spectrometer, allowing for simultaneous APXPS and IR spectroscopy of the samples. The endstation is set up to easily accommodate further sample environments.

Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation.

PURPOSE: Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations. METHODS: Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data. RESULTS: A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia, hepatosplenomegaly, autoimmune thyroiditis, and severe autoimmune gastrointestinal manifestations. Immunological investigations revealed low immunoglobulin levels and low numbers of B and NK cells. Treatment included immunoglobulin replacement and immunosuppressive therapy. Seven years after disease onset, the patient developed severe neurological symptoms resembling acute disseminated encephalomyelitis, prompting allogeneic hematopoietic stem cell transplantation (HSCT) with the HLA-identical mother as donor. Whole exome sequencing of the patient uncovered a homozygous 1 bp deletion in LRBA (c.7162delA:p.T2388Pfs*7). Importantly, during 2 years of follow-up post-HSCT, marked clinical improvement and recovery of immune function was observed. CONCLUSIONS: Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.

An XPS Study of Electrolytes for Li-Ion Batteries in Full Cell LNMO vs Si/Graphite.

Two different types of electrolytes (co-solvent and multi-salt) are tested for use in high voltage LiNi0.5Mn1.5O4||Si/graphite full cells and compared against a carbonate-based standard LiPF6 containing electrolyte (baseline). Ex situ postmortem XPS analysis on both anodes and cathodes over the life span of the cells reveals a continuously growing SEI and CEI for the baseline electrolyte. The cells cycled in the co-solvent electrolyte exhibited a relatively thick and long-term stable CEI (on LNMO), while a slowly growing SEI was determined to form on the Si/graphite. The multi-salt electrolyte offers more inorganic-rich SEI/CEI while also forming the thinnest SEI/CEI observed in this study. Cross-talk is identified in the baseline electrolyte cell, where Si is detected on the cathode, and Mn is detected on the anode. Both the multi-salt and co-solvent electrolytes are observed to substantially reduce this cross-talk, where the co-solvent is found to be the most effective. In addition, Al corrosion is detected for the multi-salt electrolyte mainly at its end-of-life stage, where Al can be found on both the anode and cathode. Although the co-solvent electrolyte offers superior interface properties in terms of the limitation of cross-talk, the multi-salt electrolyte offers the best overall performance, suggesting that interface thickness plays a superior role compared to cross-talk. Together with their electrochemical cycling performance, the results suggest that multi-salt electrolyte provides a better long-term passivation of the electrodes for high-voltage cells.

Conservative treatment of chronic pancreatitis.

BACKGROUND: Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. AIM: This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. RESULTS: Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. CONCLUSIONS: Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines.

Potentials in Li-Ion Batteries Probed by Operando Ambient Pressure Photoelectron Spectroscopy.

The important electrochemical processes in a battery happen at the solid/liquid interfaces. Operando ambient pressure photoelectron spectroscopy (APPES) is one tool to study these processes with chemical specificity. However, accessing this crucial interface and identifying the interface signal are not trivial. Therefore, we present a measurement setup, together with a suggested model, exemplifying how APPES can be used to probe potential differences over the electrode/electrolyte interface, even without direct access to the interface. Both the change in electron electrochemical potential over the solid/liquid interface, and the change in Li chemical potential of the working electrode (WE) surface at Li-ion equilibrium can be probed. Using a Li4Ti5O12 composite as a WE, our results show that the shifts in kinetic energy of the electrolyte measured by APPES can be correlated to the electrochemical reactions occurring at the WE/electrolyte interface. Different shifts in kinetic energy are seen depending on if a phase transition reaction occurs or if a single phase is lithiated. The developed methodology can be used to evaluate charge transfer over the WE/electrolyte interface as well as the lithiation/delithiation mechanism of the WE.

Probing Electrochemical Potential Differences over the Solid/Liquid Interface in Li-Ion Battery Model Systems.

The electrochemical potential difference (ΔµÌ…) is the driving force for the transfer of a charged species from one phase to another in a redox reaction. In Li-ion batteries (LIBs), ΔµÌ… values for both electrons and Li-ions play an important role in the charge-transfer kinetics at the electrode/electrolyte interfaces. Because of the lack of suitable measurement techniques, little is known about how ΔµÌ… affects the redox reactions occurring at the solid/liquid interfaces during LIB operation. Herein, we outline the relations between different potentials and show how ambient pressure photoelectron spectroscopy (APPES) can be used to follow changes in ΔµÌ…e over the solid/liquid interfaces operando by measuring the kinetic energy (KE) shifts of the electrolyte core levels. The KE shift versus applied voltage shows a linear dependence of ∼1 eV/V during charging of the electrical double layer and during solid electrolyte interphase formation. This agrees with the expected results for an ideally polarizable interface. During lithiation, the slope changes drastically. We propose a model to explain this based on charge transfer over the solid/liquid interface.

European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations.

The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.

A 2-yr national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use.

The aim was to investigate triggering factors and insulin pump usage (continuous subcutaneous insulin infusion, CSII) at diabetic ketoacidosis (DKA). Data from 1999 and 2000 were collected retrospectively from Sweden. In 1999 and 2000, 7.4 and 11.0%, respectively, of children with diabetes used CSII. One hundred and forty-two episodes of DKA (pH < 7.30) were identified in 115 children (DKA at onset not included). Their hemoglobin A1c (HbA1c) was 10.1 +/- 2.0%, age 14.6 +/- 3.1 yr (range 1.5-19.9 yr), and diabetes duration 6.6 +/- 3.5 yr (range 0.4-17.7 yr). Fourteen persons (seven girls) had more than one episode of DKA. Reported causes of DKA were missed insulin doses (48.6%), gastroenteritis (14.1%), technical pump problems (12.7%), infection (13.4%), social problems (1.4%), unknown (5.6%), and not stated (4.2%). Alcohol was involved in eight episodes and drugs in one. Thirty of 115 patients (19 girls) used insulin pumps. The overall DKA incidence was 1.4/100 patient years in 1999 and 1.7/100 patient years in 2000. For insulin pump users, the DKA incidence was 3.2/100 patient years in 1999 and 3.6/100 patient years in 2000. HbA1c at DKA admission was lower for CSII users than patients who used injections (9.1 +/- 1.5 vs. 10.8 +/- 2.2%, p < 0.01), but pH and age did not differ. CSII had been used for 6 months (median) before the DKA episode. In conclusion, the DKA frequency in CSII users was approximately twice that of patients who used injections. Seventy-seven percent of the episodes occurred within 1 yr after CSII start. The high number of events reported to be caused by gastroenteritis is alarming because this may reflect a misinterpretation of DKA symptoms.

Cerebral venous thrombosis and heparin-induced thrombocytopenia in an 18-year old male with severe ulcerative colitis.

The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin, developed heparin-induced thrombocytopenia (HIT). The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor X.

Acute pancreatitis as a complication of childhood cancer treatment.

Acute pancreatitis (AP) is now well recognized as a possible complication of childhood cancer treatment, interrupting the chemotherapy regimen, and requiring prolonged hospitalization, possibly with intensive care and surgical intervention, thereby compromising the effect of chemotherapy and the remission of the underlying malignant disease. This review summarizes the current literature and presents the various etiological factors for AP during chemotherapy as well as modern trends in the diagnosis and therapy of AP in children.

Electric Potential Gradient at the Buried Interface between Lithium-Ion Battery Electrodes and the SEI Observed Using Photoelectron Spectroscopy.

The buried interface between the bulk electrode material and the solid electrolyte interphase (SEI) in cycled Li-ion battery anodes is suggested to incorporate an electric potential gradient. This suggestion is based on photoelectron spectroscopy (PES) results from different anode materials that all show relative binding energy shifts between the components of the SEI and the active anode. Implications of this electric potential gradient on binding energy reference points in PES as well as on charge-transfer kinetics in Li-ion batteries are discussed. Specifically, we show that the separation of surface layer and bulk material spectral contributions (depth profiling) is crucial for consistent data interpretation. We conclude that previous interpretations of lithiation as cause for changes in PES spectra may need to be revised.

Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis.

AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn(®) granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10). RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12. CONCLUSION: Adacolumn(®) GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

SEI Formation and Interfacial Stability of a Si Electrode in a LiTDI-Salt Based Electrolyte with FEC and VC Additives for Li-Ion Batteries.

An electrolyte based on the new salt, lithium 4,5-dicyano-2-(trifluoromethyl)imidazolide (LiTDI), is evaluated in combination with nano-Si composite electrodes for potential use in Li-ion batteries. The additives fluoroethylene carbonate (FEC) and vinylene carbonate (VC) are also added to the electrolyte to enable an efficient SEI formation. By employing hard X-ray photoelectron spectroscopy (HAXPES), the SEI formation and the development of the active material is probed during the first 100 cycles. With this electrolyte formulation, the Si electrode can cycle at 1200 mAh g(-1) for more than 100 cycles at a coulombic efficiency of 99%. With extended cycling, a decrease in Si particle size is observed as well as an increase in silicon oxide amount. As opposed to LiPF6 based electrolytes, this electrolyte or its decomposition products has no side reactions with the active Si material. The present results further acknowledge the positive effects of SEI forming additives. It is suggested that polycarbonates and a high LiF content are favorable components in the SEI over other kinds of carbonates formed by ethylene carbonate (EC) and dimethyl carbonate (DMC) decomposition. This work thus confirms that LiTDI in combination with the investigated additives is a promising salt for Si electrodes in future Li-ion batteries.

Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes.

OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.

Can pulmonary hypertension and increased pulmonary vascular resistance be ruled in and ruled out by echocardiography?

BACKGROUND: Several treatment options are available for pulmonary vascular disease, and more patients are considered for right heart catheterization. The aims of this study were to evaluate the diagnostic ability of echocardiography to detect pulmonary hypertension and increased pulmonary vascular resistance (PVR). METHODS: This retrospective study comprised 118 patients investigated within 48 hours of right heart catheterization. Echocardiography was used to assess pulmonary artery systolic pressure and pulmonary artery mean pressure, filling pressures, cardiac output, and PVR. To diagnose increased PVR, three echocardiographic variables related to pressure reflection in the pulmonary circulation were used. Separate cutoff values aimed at ruling in (high positive likelihood ratio [PLR]) and ruling out (low negative likelihood ratio) pulmonary hypertension (pulmonary artery mean pressure >25 mm Hg) and increased PVR (>3 Wood units) were determined from a derivation group (n = 59, receiver operating characteristic curve analysis) and evaluated in a test group (n = 59). RESULTS: The linear relations between hemodynamic variables assessed with simultaneous echocardiography and right heart catheterization were moderate to strong (R = 0.55 to 0.95), and there were no significant differences, but the limits of agreement were wide. With Doppler pulmonary artery systolic pressure >39 mm Hg, the PLR for pulmonary artery mean pressure >25 mm Hg was 4.7, and with Doppler pulmonary artery systolic pressure ≤29 mm Hg, the negative likelihood ratio was 0.12. The PLR for pressure reflection variables with ruling-in cutoff values ranged from 4.3 to 6.4. With all three variables positive, the PLR was 9.9. The negative likelihood ratio with ruling-out cutoff values ranged from 0.22 to 0.08. CONCLUSIONS: Echocardiography that includes assessment of pressure reflection in the pulmonary circulation can rule in and rule out pulmonary hypertension and increased PVR.

Echocardiography can identify patients with increased pulmonary vascular resistance by assessing pressure reflection in the pulmonary circulation.

BACKGROUND: Pulmonary hypertension is a frequent finding in patients with cardiopulmonary disorders. It is important to recognize pulmonary hypertension due to increased pulmonary vascular resistance (PVR), as this affects treatment and prognosis. Patients with increased PVR have an increased pulmonary pressure reflection. We hypothesized that pressure reflection can be described by echocardiography and that variables related to pressure reflection can identify patients with increased PVR. METHODS AND RESULTS: The study comprised 98 patients investigated within 24 hours of right heart catheterization and 20 control subjects. The pressure reflection variables were obtained by pulsed Doppler in the pulmonary artery and continuous Doppler of tricuspid regurgitation. We selected 3 variables related to pressure reflection: the interval from valve opening to peak velocity in the pulmonary artery (AcT, ms), the interval between pulmonary artery peak velocity and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the pulmonary artery (augmented pressure, AP, mm Hg). The correlation between simultaneous catheter- and echocardiography-determined AP was strong (n=19, R=0.83). The AcT, tPV-PP, and AP in patients with a PVR of >3 Woods units (n=71) was (mean+/-SD) 77+/-16 ms, 119+/-36 ms, and 22+/-12 mm Hg, respectively, and differed from patients with a PVR of