Recent data on isoscalar giant monopole resonance (ISGMR) in the calcium isotopes 40,44,48Ca have suggested that Kτ, the asymmetry term in the nuclear incompressibility, has a positive value. A value ...of Kτ>0 is entirely incompatible with present theoretical frameworks and, if correct, would have far-reaching implications on our understanding of myriad nuclear and astrophysical phenomena. This paper presents results of an independent ISGMR measurement with the 40,42,44,48Ca(α,α′) reaction at Eα=386 MeV. These results conclusively discount the possibility of a positive value for Kτ, and are consistent with the previously-obtained values for this quantity.
“Why are the tin isotopes soft?” has remained, for the past decade, an open problem in nuclear structure physics: models which reproduce the isoscalar giant monopole resonance (ISGMR) in the ...“doubly-closed shell” nuclei, 90Zr and 208Pb, overestimate the ISGMR energies of the open-shell tin and cadmium nuclei, by as much as 1 MeV. In an effort to shed some light onto this problem, we present results of detailed studies of the ISGMR in the molybdenum nuclei, with the goal of elucidating where–and how–the softness manifests itself between 90Zr and the cadmium and tin isotopes. The experiment was conducted using the 94,96,98,100Mo(α,α′) reaction at Eα=386 MeV. A comparison of the results with relativistic, self-consistent Random-Phase Approximation calculations indicates that the ISGMR response begins to show softness in the molybdenum isotopes beginning with A=92.
Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of ...circulating proteins.
To quantify and analyze the plasma proteome of patients with PAH using inherited genetic variation to inform on underlying molecular drivers.
An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers, and 23 relatives of patients with PAH. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared, and the relationship to transplantation-free survival in PAH was determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomization (MR) analysis.
From 4,152 annotated plasma proteins, levels of 208 differed between patients with PAH and healthy subjects, and 49 predicted long-term survival. MR based on
-pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio OR, 1.55; 95% confidence interval CI, 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR, 0.83; 95% CI, 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset.
Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH.
We have investigated the temperature-dependent roughening kinetics of Ge surfaces during low energy ion sputtering using energy dispersive x-ray reflectivity. At 150 degreeC and below, the surface is ...amorphized by ion impact and roughens to a steady state small value. At 250 degreeC the surface remains crystalline, roughens exponentially with time, and develops a pronounced ripple topography. At higher temperature this exponential roughening is slower, with an initial sublinear time dependence. A model that contains a balance between smoothing by surface diffusion and viscous flow and roughening by atom removal explains the kinetics. Ripple formation is a result of a curvature-dependent sputter yield.
The rare phenomenon of nuclear wobbling motion has been investigated in the nucleus ^{187}Au. A longitudinal wobbling-bands pair has been identified and clearly distinguished from the associated ...signature-partner band on the basis of angular distribution measurements. Theoretical calculations in the framework of the particle rotor model are found to agree well with the experimental observations. This is the first experimental evidence for longitudinal wobbling bands where the expected signature partner band has also been identified, and establishes this exotic collective mode as a general phenomenon over the nuclear chart.
Nitrite anions comprise the largest vascular storage pool of nitric oxide (NO), provided that physiological mechanisms exist to reduce nitrite to NO. We evaluated the vasodilator properties and ...mechanisms for bioactivation of nitrite in the human forearm. Nitrite infusions of 36 and 0.36 micromol/min into the forearm brachial artery resulted in supra- and near-physiologic intravascular nitrite concentrations, respectively, and increased forearm blood flow before and during exercise, with or without NO synthase inhibition. Nitrite infusions were associated with rapid formation of erythrocyte iron-nitrosylated hemoglobin and, to a lesser extent, S-nitroso-hemoglobin. NO-modified hemoglobin formation was inversely proportional to oxyhemoglobin saturation. Vasodilation of rat aortic rings and formation of both NO gas and NO-modified hemoglobin resulted from the nitrite reductase activity of deoxyhemoglobin and deoxygenated erythrocytes. This finding links tissue hypoxia, hemoglobin allostery and nitrite bioactivation. These results suggest that nitrite represents a major bioavailable pool of NO, and describe a new physiological function for hemoglobin as a nitrite reductase, potentially contributing to hypoxic vasodilation.
To determine whether an advanced cardiac life support (ACLS) computer simulation program improves retention of ACLS guidelines more effectively than textbook review.
Randomized, controlled trial.
...Academic medical center.
Forty-five anesthesia residents and faculty tested 10 to 11 months after ACLS provider course training.
Participants were randomized and asked to prepare for a mock resuscitation (Mega Code) with either textbooks or a computerized ACLS simulation program.
Performance on a standardized Mega Code examination that required application of supraventricular tachycardia, ventricular fibrillation, and second-degree Type II atrioventricular block algorithms. Mega Code sessions were administered by an instructor who was blinded as to the subject group. The sessions were videotaped and scored by two evaluators who also were blinded as to the subject group.
Participants who used the ACLS simulation program scored significantly higher (mean 34.9 +/- 5.0 SD of 47 possible points) than participants who reviewed using a textbook (29.2 +/- 4.9); p < .001. Pass-fail rates for the algorithms were also higher for the group that reviewed with the simulator (mean 2.5 +/- 0.5 of 3 possible passes) than the group that used the textbook (1.6 +/- 1.0); p = .001.
Use of a computerized ACLS simulation program improves retention of ACLS guidelines better than textbook review.
Patients with adult-onset growth hormone deficiency have reduced bone density and increased fat mass. Growth hormone at high doses may decrease body fat in these patients, but the effects of growth ...hormone at more physiologic doses on bone density and body composition have not been convincingly shown.
To determine whether long-term growth hormone therapy at a dose adjusted to maintain normal insulin-like growth factor 1 (IGF-1) levels has clinical effects in patients with adult-onset growth hormone deficiency.
Randomized, placebo-controlled study.
Tertiary referral center.
32 men with adult-onset growth hormone deficiency.
Growth hormone (initial daily dose, 10 micrograms/kg of body weight) or placebo for 18 months. The growth hormone dose was reduced by 25% if IGF-1 levels were elevated.
Body composition and bone mineral density of the lumbar spine, femoral neck, and proximal radius were measured by dual energy x-ray absorptiometry at 6-month intervals. Markers of bone turnover were also measured during the first 12 months of the study.
Growth hormone therapy increased bone mineral density in the lumbar spine by a mean (+/- SD) of 5.1% +/- 4.1% and bone mineral density in the femoral neck by 2.4% +/- 3.5%. In the growth hormone group, significant increases were seen in the following markers of bone turnover: osteocalcin (4.4 +/- 3.6 mg/L to 7.2 +/- 4.6 mg/L) and urinary pyridinoline (39.0 +/- 19.8 nmol/mmol of creatinine to 55.7 +/- 25.5 nmol/mmol of creatinine) and deoxypyridinoline (8.4 +/- 7.1 nmol/mmol of creatinine to 14.9 +/- 9.4 nmol/mmol of creatinine). Percentage of body fat in the growth hormone group decreased (from 31.9% +/- 6.5% to 28.3% +/- 7.0%), and lean body mass increased (from 59.0 +/- 8.5 kg to 61.5 +/- 6.9 kg). These changes were significant compared with corresponding changes in the placebo group (P < 0.01 for all comparisons).
Growth hormone administered to men with adult-onset growth hormone deficiency at a dose adjusted according to serum IGF-1 levels increases bone density and stimulates bone turnover, decreases body fat and increases lean mass, and is associated with a low incidence of side effects.
GPR40 is a member of a subfamily of homologous G protein-coupled receptors that include GPR41 and GPR43 and that have no current function or ligand ascribed. Ligand fishing experiments in HEK293 ...cells expressing human GPR40 revealed that a range of saturated and unsaturated carboxylic acids with carbon chain lengths greater than six were able to induce an elevation of Ca(2+)(i), measured using a fluorometric imaging plate reader. 5,8,11-Eicosatriynoic acid was the most potent fatty acid tested, with a pEC(50) of 5.7. G protein coupling of GPR40 was examined in Chinese hamster ovary cells expressing the G alpha(q/i)-responsive Gal4-Elk1 reporter system. Expression of human GPR40 led to a constitutive induction of luciferase activity, which was further increased by exposure of the cells to eicosatriynoic acid. Neither the constitutive nor ligand-mediated luciferase induction was inhibited by pertussis toxin treatment, suggesting that GPR40 was coupled to G alpha(q/11.) Expression analysis by quantitative reverse transcription-PCR showed that GPR40 was specifically expressed in brain and pancreas, with expression in rodent pancreas being localized to insulin-producing beta-cells. These data suggest that some of the physiological effects of fatty acids in pancreatic islets and brain may be mediated through a cell-surface receptor.
To evaluate the Johns Hopkins Hospital experience with 136 thymomas over the past 40 years. This number of patients allowed quantitative estimation of the independent influence of common ...clinicopathologic risk factors using multivariate analysis.
Thymomas vary widely in terms of recurrence and influence on overall survival. Several series have indicated the importance of initial tumor invasion, as well as the extent of surgical resection, as predictors of recurrence and survival after thymoma resection. However, findings have been equivocal when other predictors of prognosis were examined.
The authors evaluated 136 patients seen at the Johns Hopkins Hospital between 1957 and 1997 with a pathologic diagnosis of thymoma. Demographic information, clinical staging data, surgical and adjuvant treatment details, and patient follow-up data were obtained from the patient record and from detailed patient or family interviews. Microscopic sections of all 136 patients were reviewed by two pathologists blinded to the clinical data. All data were analyzed by multivariate Cox regression analysis, which allowed the quantification of the independent predictive value of 12 putative clinicopathologic prognostic indicators.
Completeness of follow-up was 99%, 99%, and 98% of eligible patients at 5, 10, and 15 years, respectively. Forty percent of the patients had associated myasthenia gravis and 27% had a secondary primary malignancy. Overall patient survival rates were 71%, 56%, 44%, 38%, and 33% at 5, 10, 15, 20, and 25 years, respectively. Overall, the thymoma-related mortality rate was 14%; the nonthymoma-related mortality rate was 26%. Incomplete resection, preoperative absence of myasthenia gravis, and advanced Lattes/Bernatz pathologic class were found to be independent predictors of poorer overall survival.
These findings support a policy of aggressive, complete surgical resection of all thymomas when feasible. Thymoma behaves as a rather indolent tumor, with most deaths from causes unrelated to thymoma or its direct treatment. Clinicians should have an increased awareness of the possibility of second primary malignancies in patients with thymoma.
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