Improved clinical utility of preimplantation genetic testing through the integration of ploidy and common pathogenic microdeletions analyses.

STUDY QUESTION: Can chromosomal abnormalities beyond copy-number aneuploidies (i.e. ploidy level and microdeletions (MDs)) be detected using a preimplantation genetic testing (PGT) platform? SUMMARY ANSWER: The proposed integrated approach accurately assesses ploidy level and the most common pathogenic microdeletions causative of genomic disorders, expanding the clinical utility of PGT. WHAT IS KNOWN ALREADY: Standard methodologies employed in preimplantation genetic testing for aneuploidy (PGT-A) identify chromosomal aneuploidies but cannot determine ploidy level nor the presence of recurrent pathogenic MDs responsible for genomic disorders. Transferring embryos carrying these abnormalities can result in miscarriage, molar pregnancy, and intellectual disabilities and developmental delay in offspring. The development of a testing strategy that integrates their assessment can resolve current limitations and add valuable information regarding the genetic constitution of embryos, which is not evaluated in PGT providing new level of clinical utility and valuable knowledge for further understanding of the genomic causes of implantation failure and early pregnancy loss. To the best of our knowledge, MDs have never been studied in preimplantation human embryos up to date. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort analysis including blastocyst biopsies collected between February 2018 and November 2021 at multiple collaborating IVF clinics from prospective parents of European ancestry below the age of 45, using autologous gametes and undergoing ICSI for all oocytes. Ploidy level determination was validated using 164 embryonic samples of known ploidy status (147 diploids, 9 triploids, and 8 haploids). Detection of nine common MD syndromes (-4p=Wolf-Hirschhorn, -8q=Langer-Giedion, -1p=1p36 deletion, -22q=DiGeorge, -5p=Cri-du-Chat, -15q=Prader-Willi/Angelman, -11q=Jacobsen, -17p=Smith-Magenis) was developed and tested using 28 positive controls and 97 negative controls. Later, the methodology was blindly applied in the analysis of: (i) 100 two pronuclei (2PN)-derived blastocysts that were previously defined as uniformly euploid by standard PGT-A; (ii) 99 euploid embryos whose transfer resulted in pregnancy loss. PARTICIPANTS/MATERIALS, SETTING, METHODS: The methodology is based on targeted next-generation sequencing of selected polymorphisms across the genome and enriched within critical regions of included MD syndromes. Sequencing data (i.e. allelic frequencies) were analyzed by a probabilistic model which estimated the likelihood of ploidy level and MD presence, accounting for both sequencing noise and population genetics patterns (i.e. linkage disequilibrium, LD, correlations) observed in 2504 whole-genome sequencing data from the 1000 Genome Project database. Analysis of phased parental haplotypes obtained by single-nucleotide polymorphism (SNP)-array genotyping was performed to confirm the presence of MD. MAIN RESULTS AND THE ROLE OF CHANCE: In the analytical validation phase, this strategy showed extremely high accuracy both in ploidy classification (100%, CI: 98.1-100%) and in the identification of six out of eight MDs (99.2%, CI: 98.5-99.8%). To improve MD detection based on loss of heterozygosity (LOH), common haploblocks were analyzed based on haplotype frequency and LOH occurrence in a reference population, thus developing two further mathematical models. As a result, chr1p36 and chr4p16.3 regions were excluded from MD identification due to their poor reliability, whilst a clinical workflow which incorporated parental DNA information was developed to enhance the identification of MDs. During the clinical application phase, one case of triploidy was detected among 2PN-derived blastocysts (i) and one pathogenic MD (-22q11.21) was retrospectively identified among the biopsy specimens of transferred embryos that resulted in miscarriage (ii). For the latter case, family-based analysis revealed the same MD in different sibling embryos (n = 2/5) from non-carrier parents, suggesting the presence of germline mosaicism in the female partner. When embryos are selected for transfer based on their genetic constitution, this strategy can identify embryos with ploidy abnormalities and/or MDs beyond aneuploidies, with an estimated incidence of 1.5% (n = 3/202, 95% CI: 0.5-4.5%) among euploid embryos. LIMITATIONS, REASONS FOR CAUTION: Epidemiological studies will be required to accurately assess the incidence of ploidy alterations and MDs in preimplantation embryos and particularly in euploid miscarriages. Despite the high accuracy of the assay developed, the use of parental DNA to support diagnostic calling can further increase the precision of the assay. WIDER IMPLICATIONS OF THE FINDINGS: This novel assay significantly expands the clinical utility of PGT-A by integrating the most common pathogenic MDs (both de novo and inherited ones) responsible for genomic disorders, which are usually evaluated at a later stage through invasive prenatal testing. From a basic research standpoint, this approach will help to elucidate fundamental biological and clinical questions related to the genetics of implantation failure and pregnancy loss of otherwise euploid embryos. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. S.C., M.F., F.C., P.Z., I.P., L.G., C.P., M.P., D.B., J.J.-A., D.B.-J., J.M.-V., and C.R. are employees of Igenomix and C.S. is the head of the scientific board of Igenomix. A.C. and L.P. are employees of JUNO GENETICS. Igenomix and JUNO GENETICS are companies providing reproductive genetic services. TRIAL REGISTRATION NUMBER: N/A.

Clinical validity and utility of preconception expanded carrier screening for the management of reproductive genetic risk in IVF and general population.

STUDY QUESTION: What is the clinical validity and utility of preconception Expanded Carrier Screening (ECS) application on the management of prospective parents? SUMMARY ANSWER: The high detection rate of at-risk couples (ARCs) and the high proportion opting for IVF/preimplantation genetic testing (PGT) treatment demonstrate the clinical utility of ECS in the preconception space in IVF and general population. WHAT IS KNOWN ALREADY: About 2-4% of couples are at risk of conceiving a child with an autosomal recessive or X-linked genetic disorder. In recent years, the increasing cost-effectiveness of genetic diagnostic techniques has allowed the creation of ECS panels for the simultaneous detection of multiple recessive disorders. Comprehensive preconception genetic screening holds the potential to significantly improve couple's genetic risk assessment and reproductive planning to avoid detectable inheritable genetic offspring. STUDY DESIGN, SIZE, DURATION: A total of 3877 individuals without a family history of genetic conditions were analyzed between January 2017 and January 2020. Of the enrolled individuals, 1212 were gamete donors and 2665 were patients planning on conceiving from both the IVF and the natural conception group. From the non-donor cohort, 1133 were analyzed as individual patients, while the remaining ones were analyzed as couples, for a total of 766 couples. PARTICIPANTS/MATERIALS, SETTING, METHODS: A focused ECS panel was developed following American College of Obstetrics and Gynecology ACOG-recommended criteria (prevalence, carrier rate, severity), including highly penetrant severe childhood conditions. Couples were defined at-risk when both partners carried an autosomal recessive pathogenic/likely pathogenic variant (PLP) on the same gene or when the woman was a carrier of an X-linked PLP variant. ARC detection rate defined the clinical validity of the ECS approach. Clinical utility was evaluated by monitoring ARCs reproductive decision making. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 402 individuals (10.4%) showed PLP for at least one of the genes tested. Among the 766 couples tested, 173 showed one carrier partner (22.6%), whereas 20 couples (2.6%) were found to be at increased risk. Interestingly, one ARC was identified as a result of cascade testing in the extended family of an individual carrying a pathogenic variant on the Survival Of Motor Neuron 1SMN1 gene. Of the identified ARCs, 5 (0.7%) were at risk for cystic fibrosis, 5 (0.7%) for fragile X syndrome, 4 (0.5%) for spinal muscular atrophy, 4 (0.5%) for Beta-Thalassemia/Sickle Cell Anemia, 1 (0.1%) for Smith-Lemli-Opitz Syndrome and 1 (0.1%) for Duchenne/Becker Dystrophy. Fifteen ARCs were successfully followed up from both the IVF and the natural conception groups. All of these (15/15) modified their reproductive planning by undergoing ART with Preimplantation Genetic Testing for Monogenic disease and Aneuploidies (PGT-M and PGT-A). To date, 6/15 (40%) couples completed their PGT cycle with euploid/unaffected embryos achieving a pregnancy after embryo transfer and three of them have already had an unaffected baby. LIMITATIONS, REASONS FOR CAUTION: The use of a limited panel of core gene-disease pairs represents a limitation on the research perspective as it can underestimate the rate of detectable carriers and ARCs in this cohort of prospective parents. Expanding the scope of ECS to a larger panel of conditions is becoming increasingly feasible, thanks to a persistent technological evolution and progressive cataloging of gene-disease associations. WIDER IMPLICATIONS OF THE FINDINGS: These results highlight the potential clinical validity and utility of ECS in reducing the risk of a pregnancy affected by a detectable inheritable genetic condition. The steady reduction in the costs of genetic analyses enables the expansion of monogenic testing/screening applications at the preimplantation stage, thus, providing valid decisional support and reproductive autonomy to patients, particularly in the context of IVF. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. A.C., M.F., S.C., M.P., L.G., and C.P. are employees of Igenomix Italy. C.S. is the head of the scientific board of Igenomix. TRIAL REGISTRATION NUMBER: N/A.

Cerebrospinal-fluid drain-related complications in patients undergoing open and endovascular repairs of thoracic and thoraco-abdominal aortic pathologies: a systematic review and meta-analysis.

BACKGROUND: Cerebrospinal-fluid (CSF) drainage is recommended by current guidelines for spinal protection during open and endovascular repairs of thoracic and thoraco-abdominal aortic aneurysms. In the published literature, great variability exists in the rate of CSF-related complications and morbidity. Herein, we perform a systematic review and meta-analysis on the incidence of CSF drainage-related complications, and compare the complication rates between open and endovascular repairs. METHODS: The systematic review was conducted according to the Meta-Analysis of Observational Studies in Epidemiology guidelines. Thirty-four studies (4714 patients) were included in the quantitative analysis. The CSF drainage-related complications were categorised as mild, moderate, and severe. Pooled event rates for each complication category were estimated using a random-effect model. Random-effect uni- and multivariable meta-regression analyses were used to assess the effect of aortic-repair approach (open vs endovascular) and the CSF drainage criteria on CSF drainage-related complications. RESULTS: The pooled event rates were 6.5% [95% confidence interval (CI): 4.3-9.8%] for overall complications, 2% (95% CI: 1.1-3.4%) for minor complications, 3.7% (95% CI: 2.5-5.6%) for moderate complications, and 2.5% (95% CI: 1.6-3.8%) for severe complications. The drainage-related-mortality pooled event rate was 0.9% (95% CI: 0.6-1.4%). The uni- and multivariable meta-regression analyses showed no difference in complication rates between the open and endovascular approaches, or between the different CSF drainage protocols. CONCLUSION: The complication rate for CSF drainage is not negligible. Our results help define a more accurate risk-benefit ratio for CSF drain placement at the time of repair of thoracic and thoraco-abdominal aneurysms.

Effect of Interfacial SiOx Defects on the Functional Properties of Si-Transition Metal Oxide Photoanodes for Water Splitting.

The transfer of photogenerated charges through interfaces in heterojunction photoanodes is a key process that controls the efficiency of solar water splitting. Considering Co3O4/SiOx/Si photoanodes prepared by physical vapor deposition as a representative case study, it is shown that defects normally present in the native SiOx layer dramatically affect the onset of the photocurrent. Electron paramagnetic resonance indicates that the signal of defects located in dangling bonds of trivalent Si atoms at the Si/SiOx interface vanishes upon vacuum annealing at 850 °C. Correspondingly, the photovoltage of the photoanode increases to ≈500 mV. Similar results are obtained for NiO/SiOx/Si photoanodes. Photoelectrochemical analysis and impedance spectroscopy (in solution and in the solid state) indicate how the defect annealing modifies the Co3O4/SiOx/Si junction. This work shows that defect annealing at the solid-solid interface in composite photoanodes strongly improves the efficiency of charge transfer through interfaces, which is the basis for effective solar-to-chemical energy conversion.

Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells.

Bone marrow (BM)-derived circulating endothelial precursor cells (CEPs) are thought to play a role in postnatal angiogenesis. Emerging evidence suggests that angiogenic stress of vascular trauma may induce mobilization of CEPs to the peripheral circulation. In this regard, we studied the kinetics of CEP mobilization in two groups of patients who experienced acute vascular insult secondary to burns or coronary artery bypass grafting (CABG). In both burn and CABG patients, there was a consistent, rapid increase in the number of CEPs, determined by their surface expression pattern of vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial cadherin (VE-cadherin), and AC133. Within the first 6 to 12 hours after injury, the percentage of CEPs in the peripheral blood of burn or CABG patients increased almost 50-fold, returning to basal levels within 48 to 72 hours. Mobilized cells also formed late-outgrowth endothelial colonies (CFU-ECs) in culture, indicating that a small, but significant, number of circulating endothelial cells were BM-derived CEPs. In parallel to the mobilization of CEPs, there was also a rapid elevation of VEGF plasma levels. Maximum VEGF levels were detected within 6 to 12 hours of vascular trauma and decreased to baseline levels after 48 to 72 hours. Acute elevation of VEGF in the mice plasma resulted in a similar kinetics of mobilization of VEGFR2(+) cells. On the basis of these results, we propose that vascular trauma may induce release of chemokines, such as VEGF, that promotes rapid mobilization of CEPs to the peripheral circulation. Strategies to improve the mobilization and incorporation of CEPs may contribute to the acceleration of vascularization of the injured vascular tissue.

The use of chitosan modified with glutaraldehyde and glyoxal as chromatographic support for the separation of flavonoids from Aleurites moluccana leaves.

This paper describes the preparation of chitosan modified with dialdehydes, glutaraldehyde (CH-Glu) and glyoxal (CH-Gly) and its application in the isolation of the flavonoids swertisin and 2"-O-rhamnosylswertisin from A. mollucana. The additional non-polar alkyl groups increase the hydrophobicity of the sorbent. The results show that the separation was mediated by hydrophobic interaction (CH-Glu), as well as hydrogen bonding, between phenolic OH or rhamnosil residues from the flavonoids, and the free amine groups (CH-Gly).

En bloc esophagectomy improves survival for stage III esophageal cancer.

OBJECTIVE: The role of en bloc esophagectomy in the surgical treatment of patients with locally advanced esophageal cancer is not well defined. This report attempts to elucidate its impact on survival, in comparison with less extensive resection, among patients with stage III disease. METHODS: A prospectively established database was retrospectively analyzed. RESULTS: One hundred twenty-eight patients underwent esophagectomy for carcinoma of the thoracic esophagus between 1988 and 1996 (78 underwent en bloc resection and 50 underwent standard resection). The 30-day and hospital mortality rates were 3.9% and 5.4%, respectively, comparable for the two procedures. Fifty-four patients had stage III disease. Overall 4-year survival was 34.5% after en bloc resection, with a median survival of 27 months (n = 33), and 11% after standard resection (n = 21), with a median survival of 12 months (p = 0.007). Among patients with stage III disease undergoing a complete resection, 4-year survivals were 36.7% and 0% after en bloc and standard resections, respectively (p = 0.001). Eighty-six of 128 patients had nodal metastasis. Three-year survivals for patients with NI disease were 33.9% and 13% after en bloc and standard resections, respectively (p = 0.02). CONCLUSION: Among patients with stage III esophageal cancer, en bloc resection appears to significantly improve survival compared with lesser resections. This improvement in survival may be attributable to resection of nodal disease.

Improved survival after intraoperative cardiac arrest in noncardiac surgical patients.

OBJECTIVE: To test the hypothesis that improvements in intraoperative and perioperative critical care are resulting in an improved outcome after intraoperative cardiac arrest. DESIGN: A retrospective consecutive series of patients who experienced an intraoperative cardiac arrest during noncardiothoracic surgical procedures between January 1986 and June 1994. SETTING: A tertiary care university-based hospital. PARTICIPANTS: Twenty-four consecutive patients who experienced an intraoperative arrest among 162,661 noncardiothoracic surgical procedures during the designated period. INTERVENTION: Advanced cardiac life support and advanced trauma life support methods were used appropriately. Postarrest pharmacologic and mechanical cardiopulmonary support were used as needed in the setting of a surgical intensive care unit. MAIN OUTCOME MEASURES: Survival out of the operating room and survival to discharge. RESULTS: Fifteen patients (62%) were resuscitated in the operating room and taken to the surgical intensive care unit or recovery room. Nine patients (38%) survived to discharge from the hospital. Twelve arrests (50%) were primarily cardiac in origin. Predictors of mortality included a need for pressor or inotropic support (P < .001) and duration of the arrest greater than 15 minutes (P < .001). CONCLUSION: Survival from an intraoperative cardiac arrest in a noncardiothoracic surgical patient is much improved over rates in historical controls who experienced in-hospital and out-of-hospital cardiac arrest. Rapid identification and aggressive correction of mechanical and metabolic derangements is warranted.

Inflammatory aneurysm of the ascending aorta and aortic arch.

Inflammatory aortic aneurysms are distinct clinical entities seen mostly in the infrarenal abdominal aorta and rarely in the descending thoracic aorta. We present the case of a 61-year-old woman with an inflammatory aortic aneurysm of the ascending aorta and aortic arch.

Repair of traumatic aortic valve disruption and descending aortic transection.

Traumatic aortic transection after acute deceleration injury remains a highly lethal condition. Concomitant aortic valve disruption is exceedingly rare, and can complicate the timing of surgical management. This report describes the management and outcome of a patient with these types of injuries.

Repair of thoracoabdominal aortic aneurysms in octogenarians.

BACKGROUND: Reports on octogenarians undergoing coronary revascularization, valve replacement, and abdominal aneurysmorrhaphy demonstrate little increase in operative risk during elective procedures. However, the mortality in this group of patients increases rapidly when urgent or emergent procedures are performed. We analyzed the outcome of patients in their ninth decade of life undergoing repair of thoracoabdominal aortic aneurysms. METHODS: A retrospective review of 39 consecutive octogenarians undergoing repair of thoracoabdominal aortic aneurysms. RESULTS: Thirty-nine of the past 900 patients with thoracoabdominal aortic aneurysms (5.2%) repaired by us were between the ages of 80 and 89 years. The median age was 84 years with a male-to-female ratio of 1:3. Two of 39 patients (5%) had acute type III dissections, and the remainder had chronic aneurysms. Twelve patients had Crawford extent I aneurysms, whereas 7, 10, and 10 patients were extent II, III, and IV, respectively. The overall in-hospital mortality was 10.3% (4 of 39 patients). Major postoperative complications included paraperesis/paraplegia, 5% (n = 2); renal failure, 18% (n = 7) including hemodialysis in 3 patients; stroke, 5% (n = 2); myocardial infarction or arrhythmia, 18% (n = 7); and respiratory insufficiency, 36% (n = 14) including 4 patients requiring tracheostomy. A univariate analysis of perioperative risk factors was performed using the Fisher's exact test. The need for hemodialysis (p = 0.035), a tracheostomy (p = 0.0001), or a perioperative myocardial infarction (p < 0.001) significantly increased the risk of death. CONCLUSIONS: Repair of thoracoabdominal aortic aneurysms in octogenarians can be performed with acceptable morbidity and mortality. However, survival decreases dramatically with even single system organ failure. An extended period of recovery is usually required in these elderly, high-risk patients.

Aortic root replacement: results using the St. Jude Medical/Hemashield composite graft.

BACKGROUND: Aortic root replacement remains a formidable operation. Although perioperative mortality has declined steadily, there is no consensus regarding the preferred method of reconstruction or type of composite to be used. We present our last 2 years' experience with aortic root replacement using the St. Jude Medical/Hemashield composite valve conduit. METHODS: A retrospective review of 52 consecutive patients undergoing aortic root replacement from February 1994 through October 1996 is presented. Both the open/exclusion and Cabrol methods of reconstruction were used. RESULTS: Thirty-one percent of the patients had undergone previous procedures of the aortic root. Thirty-seven percent required aortic arch replacement and 35% required concomitant cardiac or vascular procedures. Perioperative morbidity was low, as was perioperative mortality (3.8%). Both of the deaths that occurred were related to complications with the management of remaining thoracoabdominal aneurysms. CONCLUSIONS: Using meticulous surgical technique and the St. Jude Medical/Hemashield composite valve conduit, one can expect low mortality and complication rates for complex aortic root reconstruction.

Pericardiocentesis and intrapericardial sclerosis: effective therapy for malignant pericardial effusions.

BACKGROUND: Pericardial effusions remain a formidable problem in patients with an advanced malignancy. We reviewed our experience with pericardiocentesis and intrapericardial sclerotherapy versus open surgical drainage as the treatment for these effusions. METHODS: A retrospective review was performed of one surgeon's experience (M.E.B.) with the surgical treatment of malignant pericardial effusions at a tertiary-care cancer center. RESULTS: Sixty patients underwent 72 procedures during 8 years. Thirty-seven (51%) pericardiocenteses and 35 (49%) open procedures were performed in patients with effusions. There was no significant difference in the complication rates seen between those effusions drained via pericardiocentesis (n = 5; 13%) and those drained in an open surgical procedure (n = 5; 14%). Similar results were seen with respect to the development of a recurrent effusion. There were no procedure-related deaths. The median survival for all patients was 97 days. Patients with breast cancer as their primary malignancy survived significantly longer after drainage than did all others (p = 0.01). The type of procedure did not influence survival. Costs of surgical drainage exceed those of pericardiocentesis by nearly fortyfold. CONCLUSIONS: Pericardiocentesis with intrapericardial sclerotherapy is as effective as open surgical drainage for the management of malignant pericardial effusions.

Recurrent systemic embolization caused by aortic thrombi.

The aorta is a commonly unrecognized source of systemic embolization. Transesophageal echocardiography is a reliable method for visualization of the intima of the thoracic aorta and identification of aortic thrombi. Balloon embolectomy of the aorta can be used to remove thrombi and prevent further embolic events.

Comparison of the separation of bovine heparin by strong anion exchange and by gel filtration chromatography.

Heparin has been fractionated by strong anion exchange chromatography followed by elution of the pools on a gel filtration column. This resulted in the expected inverse relationship in the elution order for the pools run by the two methods. Also chromatography of heparin was performed in the reverse order: gel filtration first, followed by anion exchange of the pools. For this order of separation four of the five gel filtration pools of different molecular weights eluted at a similar LiCl concentration. The specific activities of different pools of heparin were evaluated using a colorimetric microwell kinetics assay using antithrombin and thrombin. For the pools separated by ion exchange first, there was an exponential increase of specific activity with increasing molecular weight for all pools. For the pools isolated by gel filtration first, the specific activities became level after an initial increase in relation to molecular weight. Thus, unique pools of heparin species are being isolated by different modes of chromatography.

Isolation of flavonoids from Aleurites moluccana using chitosan modified with benzaldehyde (CH-Bz) as chromatographic support.

This paper describes the preparation, characterization and use of a derivative of chitosan as a chromatographic sorbent. Chitosan modified with benzenic ring (CH-Bz) was used to separate two flavonoids, swertisin and 2"-O-rhamnosylswertisin, from ethyl acetate fraction of Aleurites moluccana. The results showed that CH-Bz can be used as a sorbent for the separation of flavonoid compounds. The studies showed that CH-Bz in column chromatography produces goods results, separation of the flavonoid compounds.

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds.

The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0 and 73.3±5.2% for 22, 17 and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6 and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.

Perioperative intra- and extravascular volume in liver transplant recipients.

UNLABELLED: Assessing adequate volemia to avoid fluid overload and pulmonary edema perioperatively in liver transplantation (LT) is a challenge both for the anesthetist and the intensivist. Volumetric preload indices, such as intrathoracic blood volume index (ITBVI), measured by transpulmonary thermodilution, and continuous end-diastolic volume index (EDVI), measured by pulmonary artery thermodilution, were shown to better reflect preload than central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP). An ITBVI increase soon after the graft reperfusion influenced pulmonary perfusion without an alteration of extravascular lung water index (EVLWI) and without impaired oxygenation. This study was designed to evaluate relationships between CVP, PAOP, ITBVI, EDVI, and stroke volume index (SVI) within 48 hours after LT. We also investigated the relationship between EVLWI and arterial partial pressure of oxygen and inspired oxygen fraction ratio (PaO(2)/FiO(2)). METHODS: We enrolled 125 patients (103 men and 22 women) undergoing LT. All patients were monitored with the PiCCO system (Pulsion Medical System) and with advanced pulmonary artery catheter connected to the Vigilance System. Hemodynamic-volumetric data were collected upon intensive care unit admission and every 8 hours up to 48 hours. Univariate and multivariate regression models were fitted to assess associations between SVI and EDVI, ITBVI, and filling pressures after adjusting for the right ventricular ejection fraction (RVEF, categorized as ≤30, 31-40, or >40) and the phase of the observation period. We also assessed associations between PaO(2)/FiO(2) and EVLWI. RESULTS: SVI was associated with EDVI, ITBVI, and RVEF. The models showing the best fit to the data were those including EDVI and ITBVI. Neither CVP nor PAOP showed correlation with SVI. EVLWI inversely correlated with PaO(2)/FiO(2). CONCLUSIONS: In the first 48 hours after LT, ITBVI and EDVI were associated with SVI assessment, whereas CVP and PAOP were not related. EVLWI significantly inversely correlated with PaO(2)/FiO(2).

Ensemble asteroseismology of solar-type stars with the NASA Kepler mission.

In addition to its search for extrasolar planets, the NASA Kepler mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solar-type stars in the Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius, and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.