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Rare Brain Tumor Registry., [Background] Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease., [Methods] Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors., [Findings] 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18–36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47–68) at 6 months and 31% (21–42) at 2 years; overall survival was 29% (20–38) at 2 years and 27% (18–37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28–0·80; p=0·0057) and non-brainstem location (0·42 [0·22–0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16–0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19–0·67; p=0·0020), and radiotherapy (0·21, 0·10–0·41; p, [Interpretation] Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival., Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

Glycation of milk proteins and peptides can be achieved by Maillard-induced conjugation of reducing carbohydrates with the available amino groups of proteins/peptides during the early stages of the Maillard reaction. This conjugation can be achieved under wet or dry heating conditions, with the choice of heating mode influencing the rate and extent of conjugation, in addition to the functionality of the conjugated protein/peptides. Conjugation has been shown to modify the technological and nutritional properties of a range of milk protein/peptide-based ingredients. This review focuses mainly on modifications to physicochemical properties and technological functionality (i.e., solubility, heat stability, emulsification, foaming and gelation properties) of milk proteins and peptides by conjugation. Particular emphasis is placed on understanding of the relationships between changes in protein/peptide molecular structure/conformation, physicochemical properties and technological functionality, as influenced by glycation.

The impact of conjugation with maltodextrin on selected functional properties (i.e., solubility and thermal stability) of intact whey protein isolate (WPI) and whey protein hydrolysate (WPH) was determined. Conjugation of WPI and WPH (degree of hydrolysis 9.3%) with maltodextrin (MD) was achieved by heating solutions of 5% WPI or WPH with 5% MD, initial pH 8.2, at 90 °C for up to 24 h. The WPH had 55.4% higher levels of available amino groups compared with the WPI, which contributed to more rapid and extensive conjugation of WPH-MD, compared with WPI-MD. The WPI-MD and WPH-MD solutions heated for 8 h had significantly higher (P m added NaCl.

Excitotoxic insults such as cerebral ischemia are thought to enhance neuronal autophagy, which is then thought to promote neuronal cell death. Excitotoxic insults indeed increase autophagy markers. Notably, however, autophagy markers can be increased either by autophagy induction (as this enhances their production) or by late-stage autophagy inhibition (as this prevents their degradation during autophagic flux). By comparing each condition with and without protease inhibitors that prevent autophagic degradation of the autophagy markers, the results of this study show that excitotoxic glutamate increases autophagy markers by a late-stage block of autophagy. Initially, this study set out to test if the CaMKII inhibitor tatCN21 mediates its post-insult neuroprotection by regulating autophagy. While tatCN21 partially inhibited basal autophagy in hippocampal neurons, it had no effects on the already blocked autophagy after excitotoxic glutamate insults, indicating that autophagy inhibition is not its neuroprotective mechanism. Additionally, while the autophagy inhibitor chloroquine had no effect, significant neuroprotection was seen instead with two drugs that enhance autophagy induction by different mechanisms, rapamycin (mTOR-dependent) and trehalose (mTOR-independent). This suggests that therapeutic approaches should seek to enhance rather than inhibit autophagy, not only in neurodegenerative diseases (where such approach is widely accepted) but also after acute excitotoxic insults. Together, these findings significantly reshape the current view on the mutual cross-regulation of autophagy and excitotoxicity.

Objective A robust release of endothelin-1 with subsequent endothelin-A subtype receptor activation occurs in patients after cardiac surgery requiring cardiopulmonary bypass. Increased endothelin-A subtype receptor activation has been identified in patients with poor left ventricular function (reduced ejection fraction). Accordingly, this study tested the hypothesis that a selective endothelin-A subtype receptor antagonist administered perioperatively would favorably affect post-cardiopulmonary bypass hemodynamic profiles in patients with a preexisting poor left ventricular ejection fraction. Methods Patients (n = 29; 66 ± 2 years) with a reduced left ventricular ejection fraction (37% ± 2%) were prospectively randomized in a blinded fashion, at the time of elective coronary revascularization or valve replacement requiring cardiopulmonary bypass, to infusion of the highly selective and potent endothelin-A subtype receptor antagonist sitaxsentan at 1 or 2 mg/kg (intravenous bolus; n=9, 10 respectively) or vehicle (saline; n=10). Infusion of the endothelin-A subtype receptor antagonist/vehicle was performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass. Endothelin and hemodynamic measurements were performed at baseline, at separation from cardiopulmonary bypass (time 0), and at 0.5, 6, 12, and 24 hours after cardiopulmonary bypass. Results Baseline plasma endothelin (4.0 ± 0.3 fmol/mL) was identical across all 3 groups, but when compared with preoperative values, baseline values obtained from age-matched subjects with a normal left ventricular ejection fraction (n = 37; left ventricular ejection fraction > 50%) were significantly increased (2.9 ± 0.2 fmol/mL, P 05). Baseline systemic (1358 ± 83 dynes/sec/cm −5 ) and pulmonary (180 ± 23 dynes/sec/cm −5 ) vascular resistance were equivalent in all 3 groups. As a function of time 0, systemic vascular resistance changed in an equivalent fashion in the post-cardiopulmonary bypass period, but a significant endothelin-A subtype receptor antagonist effect was observed for pulmonary vascular resistance (analysis of variance; P 05). For example, at 24 hours post-cardiopulmonary bypass, pulmonary vascular resistance increased by 40 dynes/sec/cm −5 in the vehicle group but directionally decreased by more than 40 dynes/sec/cm −5 in the 2 mg/kg endothelin-A subtype receptor antagonist group ( P 05). Total adverse events were equivalently distributed across the endothelin-A subtype receptor antagonist/placebo groups. Conclusion These unique findings demonstrated that infusion of an endothelin-A subtype receptor antagonist in high-risk patients undergoing cardiac surgery was not associated with significant hemodynamic compromise. Moreover, the endothelin-A subtype receptor antagonist favorably affected pulmonary vascular resistance in the early postoperative period. Thus, the endothelin-A subtype receptor serves as a potential pharmacologic target for improving outcomes after cardiac surgery in patients with compromised left ventricular function.

A solution of the inverse heat conduction problem (IHCP) by the steepest descent method is carried out in order to determine the waste heat flux from a helicon plasma discharge using transient surface temperature measurements obtained from infrared thermography. The infrared camera data is calibrated against thermocouple data and mapped to real locations on the observed surface. The magnitude and distribution of the heat flux to the gas containment tube in the helicon is investigated as the applied power, gas flow rate, magnetic field distribution and neutral gas are varied.

Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.

Objective Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral blood was evaluated. Methods Cohorts of donor mice were treated with either progenipoietin-1, fetal liver tyrosine kinase-3 ligand, granulocyte colony-stimulating factor, or a vehicle control. Hematopoietic progenitor/stem-cell activity in donor blood was assayed by radioprotection, multilineage reconstitution, secondary transplantation, and competitive repopulation. Results Only 1 μL of peripheral blood from progenipoietin-1–treated donors was required to protect 80% of lethally irradiated mice, while in contrast 1 μL of peripheral blood from granulocyte colony-stimulating factor–treated donors failed to protect any recipients. The radioprotected recipients of progenipoietin-1–treated donor cells showed donor-derived (Ly5.2) multilineage hematopoietic reconstitution for up to 6 months. Serial transplantation studies using bone marrow from radioprotected, chimeric recipients demonstrated long-term donor-derived hematopoiesis, indicating the successful transplantation of multipotent hematopoietic stem cells. The engraftment potential of progenipoietin-1 donor-derived cells was directly compared with donors treated with granulocyte colony-stimulating factor or fetal liver tyrosine kinase-3 ligand alone or in combination. Both spleen colony-forming activity and competitive repopulating activity was highest in the blood from progenipoietin-1–treated donors. Conclusion These studies demonstrate that progenipoietin-1 is a potent mobilizer of transplantable hematopoietic stem cells and indicate that this dual-receptor agonist has greater biologic activity than its constituent molecules.

Series of rhenium catalysts were prepared by equilibrium adsorption on unmodified alumina and alumina containing F and Mg additives. The uptake of perrhenate on alumina was dependent on the pH and the concentration of nitrate in the impregnation solution. Uptake of perrhenate at pH 6.5 on F modified alumina decreased with increasing F loading; for Mg-modified aluminas, perrhenate uptake at pH 9.3 increased with increasing Mg content. A correlation was observed between perrhenate uptake and the isoelectric point (IEP) of the modified supports. These data are interpreted on the basis of electrostatic attractions which occur between perrhenate ions in solution and alumina surfaces. Competition between nitrate and perrhenate for adsorption sites satisfactorily accounts for the effect of nitrate on perrhenate adsorption.

The stability of the American economy depends on the spirit of entrepreneurship that drives the creation of new businesses, jobs, and innovations. Yet launching and running a business can involve many challenges, and many efforts fail in their early years. These barriers to success threaten our nation's long term prosperity in an increasingly competitive global economy. A new study aims to help new business owners overcome start-up challenges and build innovative, growing companies.The Ewing Marion Kauffman Foundation of Kansas City is sponsoring this research to gain a better understanding of how firms grow, strengthen, and mature. Mathematica is conducting a study of new businesses to help the Foundation in its efforts to promote new business development.The Kauffman Firm Survey (KFS) is the largest longitudinal study of new businesses ever embarked upon. The panel of businesses was created by using a random sample from Dun & Bradstreet’s (D&B) database list of new businesses started in 2004, which totaled roughly two hundred fifty-thousand such businesses. The KFS oversampled these businesses based on the intensity of research and development employment in the businesses’ primary industries. The KFS sought to create a panel that included new businesses founded by a person or team of people, purchases of existing businesses by a new ownership team, and purchases of franchises. To this end, the KFS excluded D&B records for businesses that were wholly owned subsidiaries of existing businesses, businesses inherited from someone else, and not-for-profit organizations. Also, previous research on new businesses has reported variability in how business founders perceive when their businesses started operations. Therefore, a series of questions were asked of business owners about indicators of business activity and whether these were conducted for the first time in the reference year (2004). These indicators included: Payment of state unemployment (UI) taxes, Payment of Federal Insurance Contributions Act (FICA) taxes, Presence of a legal status for the business, Use of an Employer Identification Number (EIN), Use of Schedule C to report business income on a personal tax return.To be “eligible” for the KFS, at least one of these activities had to have been performed in 2004 and none performed in a prior year. Businesses were excluded if they had an EIN, schedule C income, a legal form, or paid state UI or FICA taxes prior to 2004.

Samples containing 8% Mo and l5% W supported on magnesium- and fluoride-modified aluminas were prepared by incipient wetness impregnation and examined in the dried and calcined states using X-ray photoelectron spectroscopy (XPS, ESCA). The presence of fluoride as an additive decreased the dispersion of the Mo and W phases for dried samples. The opposite effect was observed for dried Mg-modified samples. The effects of F and Mg addition largely disappeared when the samples were calcined. The results are interpreted in terms of the interactions between Mo and W species and the basic hydroxyl groups of the alumina.

The Kauffman Firm Survey (KFS) - is the largest longitudinal study of new businesses ever embarked upon. The panel of businesses was created by using a random sample from Dun & Bradstreet’s (D&B) database list of new businesses started in 2004, which totaled roughly two hundred fifty-thousand such businesses. The KFS oversampled these businesses based on the intensity of research and development employment in the businesses’ primary industries. The KFS sought to create a panel that included new businesses founded by a person or team of people, purchases of existing businesses by a new ownership team, and purchases of franchises. To this end, the KFS excluded D&B records for businesses that were wholly owned subsidiaries of existing businesses, businesses inherited from someone else, and not-for-profit organizations. Also, previous research on new businesses has reported variability in how business founders perceive when their businesses started operations. Therefore, a series of questions were asked of business owners about indicators of business activity and whether these were conducted for the first time in the reference year (2004). These indicators included: * Payment of state unemployment (UI) taxes * Payment of Federal Insurance Contributions Act (FICA) taxes * Presence of a legal status for the business * Use of an Employer Identification Number (EIN) * Use of Schedule C to report business income on a personal tax return To be “eligible” for the KFS, at least one of these activities had to have been performed in 2004 and none performed in a prior year. Businesses were excluded if they had an EIN, schedule C income, a legal form, or paid state UI or FICA taxes prior to 2004. A random sample of 32,469 businesses was released for data collection on the baseline survey, conducted between July 2005 and July 2006. A total of 17,258 businesses were screened for eligibility, resulting in the identification of 6,030 eligible businesses (a 35% eligibility rate). Interviews were completed with principals of 4,928 businesses that started operations in 2004, which translates to a 43% weighted response rate using the American Association for Public Opinion Research (AAPOR) response rate calculation 3. A self-administered Web survey and Computer Assisted Telephone Interviewing (CATI) were used for data collection, and KFS respondents were paid $50 to complete the interview. CATI completes accounted for 3,781 (77%) and Web completes accounted for 1,147 (23%) of the total interviews. The results across sampling strata show that 2,034 interviews were completed in the two high-technology strata. The remaining 2,894 interviews were completed among non-high-tech businesses. The sample for the first follow-up survey consisted of the 4,928 businesses that completed the baseline survey. The first follow-up was conducted between June 2006 and January 2007, during which 3,998 interviews were completed and 369 businesses were identified as out of business. This translates to an 88% weighted response rate using AAPOR response rate 1. As with the baseline survey, respondents were paid $50 to complete the interview, which was offered either on the Web or through CATI. During the first follow-up, a significantly larger percentage of interviews were completed through the Web survey (2,366, or 59%) than in the baseline, with CATI completes accounting for 41% (1,632 interviews). The second follow-up survey was conducted among 4,523 KFS businesses. This included businesses that completed both the baseline and first follow-up surveys, or those not able to be interviewed during the first follow-up. Businesses identified as no longer operating during the first follow-up were excluded, as were a small number that adamantly refused to participate in the first follow-up. The second follow-up was conducted between May and December 2007, during which 3,390 interviews were completed and 406 businesses were identified as no longer operating. This translates to an 82% unweighted response rate using AAPOR response rate 1. As with the two previous surveys, respondents were paid $50 to complete the interview, which was offered either on the Web or through CATI. During the second follow-up, 63% of the interviews (2,127) were completed through the Web survey, with CATI completes accounting for 37% (1,263 interviews). The third follow-up data collection closely mirrored the collections of the first two follow-ups. Data collection began on June 24, 2008, and concluded on December 23, 2008. Some respondent fatigue was observed and a response rate dropped slightly to 78 percent (unweighted). 2,915 interviews were completed. There was a slight increase in the percentage of respondents who completed the Web survey (65 percent in the Third Follow-Up compared with 63 percent in the Second Follow-Up). For the Third Follow-Up, the ?panel maintenance packet? consisted of a colorful 2009 calendar with the study name and contact information printed on it. As with previous rounds, respondents also received a $50 incentive payment for completing the survey. Since the Baseline Survey had established eligibility for all the businesses in the panel, the only eligibility criterion for the 3,867 businesses included in the Fourth Follow-Up was whether the business was still in operation. Specifically, the remaining businesses were those that completed the Baseline Survey (4,928), minus those identified as permanently out of business during the previous followups (1,061). Businesses identified as temporarily out of business in the previous followups were included in the Fourth Follow-Up sample in case they had resumed operations since the previous interview. As in previous rounds, panel members were contacted initially by email and invited to complete the KFS web survey. Those businesses without email addresses, or those that did not respond to the initial message, were sent an invitation through U.S. mail. As in prior waves, respondents were offered a post-paid $50 incentive for completing the Fourth Follow-Up. Among the remaining eligible businesses, 2,606 interviews were completed, which resulted in a weighted response rate of 83 percent. As in the two previous follow-up surveys, most interviews were completed on the web (71 percent), the rest (29 percent) through computer-assisted telephone interviewing (CATI).

The Kauffman Firm Survey (KFS) is a panel study of new businesses founded in 2004 and tracked over their early years of operation. The survey focuses on the nature of new business formation activity; characteristics of the strategy, offerings, and employment patterns of new businesses; the nature of the financial and organizational arrangements of these businesses; and the characteristics of their founders. Download the slides at: http://papers.ssrn.com/paper=1027918 Download the audio file at: http://papers.ssrn.com/paper=1029761

The adsorption of perrhenate, permanganate, molybdate, tungstate, and chromate on alumina was studied at pH 4.5. The effect of nitrate in the impregnation solution on the adsorption of these ions was examined as well as the effect of washing the freshly prepared catalysts. The uptake of perrhenate and permanganate decreased with increasing nitrate in the impregnation solution; the uptake of molybdate, tungstate, and chromate was unaffected. Washing the catalysts almost completely removed perrhenate, permanganate, and chromate, but allowed a significant amount of molybdate and tungstate to remain on the alumina. It is concluded that tungstate and molybdate adsorb on two types of surface sites, producing loosely and tightly bound surface species. From the amounts of molybdate and tungstate adsorbed, and from EXAFS results from washed and unwashed Mo/Al2O3 samples, both loosely and tightly bound molybdate and tungstate are polymeric in nature. The results are discussed in terms of electrostatic and surface reaction models.

Achalasia of the esophagus developed in two male siblings soon after birth, and they were successfully treated by surgery. Persistent signs resulted in the later diagnosis of Hirschsprung's disease. One required subtotal colectomy and ileoanal anastomosis, and the other is managing well on conservative treatment. Genetic analysis of the genes encoding the RET protooncogene, endothelin-3, and the endothelin-3 receptor did not show any defect. Familial achalasia of the esophagus in combination with Hirschsprung's disease has never been reported.

One of the limitations in using CO[sub 2] chemisorption to monitor surface coverage is that the method is based on selective chemisorption of the catalyst support. Thus, only certain support-active phase combinations are suitable for characterization using this technique. The objective of the present study is to examine CO[sub 2] chemisorption on a wider variety of catalysts (Mo, W, V, Cr, and Re supported on Al[sub 2]O[sub 3]). Catalysts are prepared by equilibrium adsorption in order to ensure that the active phase is uniformly distributed over the support.

The isoelectric point (IEP) of γ-alumina was modified by the addition of various amounts of fluoride. The modified aluminas were used as supports for molybdenum catalysts prepared by equilibrium adsorption at pH = 6.5. Also, the adsorption of molybdate on supports containing various amounts of fluoride was studied as a function of pH. The amount of molybdenum adsorbed on the fluoride-modified aluminas was found to decrease as the IEP of the carrier decreased. An electrostatic model is used to interpret the results.

Simple boundary conditions, pressure losses, and channel geometries necessary for the unstable, rigid-body translational vibrations of the wall of a one-dimensional leakage-flow channel are identified. General expressions for the flow-damping and stiffness forces acting on the vibrating channel wall are derived and specific results are given for channels with wall friction, point pressure losses, sharp-edged constrictions, and diverging or converging widths. The minimum conditions necessary for dynamic and static (divergence) instability were found to be an upstream point pressure loss and a diverging channel width with a finite-length throat region, respectively.

The prediction of flow-induced vibrations (FIV) of structural components often must rely upon scale model test results, because direct forced response predictions are beyond the state-of-the-art. Since viscosity effects often are distorted in reduced scale model tests, the identification of fluid forces which are Reynolds number dependent is essential to the acquisition of meaningful test results. Toward this end, the fluid damping forces exerted on a vibrating tube by a surrounding narrow, fluid filled, finite length annular region are shown to be relatively larger in the model than in the prototype. A theory is proposed for estimating the magnitude of this unconservative distortion in model testing.

Analytical and experimental methods are presented for evaluating the vibration characteristics of cylindrical shells such as the thermal liner of the Fast Flux Test Facility (FFTF) reactor vessel. The NASTRAN computer program is used to calculate the natural frequencies, mode shapes, and response to a harmonic loading of a thin, circular cylindrical shell situated inside a fluid-filled rigid circular cylinder. Solutions in a vacuum are verified with an exact solution method and the SAP IV computer code. Comparisons between analysis and experiment are made, and the accuracy and utility of the fluid-solid interaction package of NASTRAN is assessed.

A completely new, very rapid, and nonirritating method of presurgical preparation of the hands and forearms has been tested in the Medical Research and Development Command at the United States Army Institute of Dental Research. This method has been shown to be superior to the conventional methods of mechanically scrubbing the hands.