Horseshoe crabs have been integral to the safe production of vaccines and injectable medications for the past 40 years. The bleeding of live horseshoe crabs, a process that leaves thousands dead ...annually, is an ecologically unsustainable practice for all four species of horseshoe crab and the shorebirds that rely on their eggs as a primary food source during spring migration. Populations of both horseshoe crabs and shorebirds are in decline. This study confirms the efficacy of recombinant Factor C (rFC), a synthetic alternative that eliminates the need for animal products in endotoxin detection. Furthermore, our findings confirm that the biomedical industry can achieve a 90% reduction in the use of reagents derived from horseshoe crabs by using the synthetic alternative for the testing of water and other common materials used in the manufacturing process. This represents an extraordinary opportunity for the biomedical and pharmaceutical industries to significantly contribute to the conservation of horseshoe crabs and the birds that depend on them.
Learning can be guided by unexpected success or failure, signaled via dopaminergic positive reward prediction error (+RPE) and negative reward-prediction error (-RPE) signals, respectively. Despite ...conflicting empirical evidence, RPE signaling is thought to be impaired in drug addiction. To resolve this outstanding question, we studied as a measure of RPE the feedback negativity (FN) that is sensitive to both reward and the violation of expectation. We examined FN in 25 healthy controls; 25 individuals with cocaine-use disorder (CUD) who tested positive for cocaine on the study day (CUD+), indicating cocaine use within the past 72 h; and in 25 individuals with CUD who tested negative for cocaine (CUD-). EEG was acquired while the participants performed a gambling task predicting whether they would win or lose money on each trial given three known win probabilities (25, 50, or 75%). FN was scored for the period in each trial when the actual outcome (win or loss) was revealed. A significant interaction between prediction, outcome, and group revealed that controls showed increased FN to unpredicted compared with predicted wins (i.e., intact +RPE) and decreased FN to unpredicted compared with predicted losses (i.e., intact -RPE). However, neither CUD subgroup showed FN modulation to loss (i.e., impaired -RPE), and unlike CUD+ individuals, CUD- individuals also did not show FN modulation to win (i.e., impaired +RPE). Thus, using FN, the current study directly documents -RPE deficits in CUD individuals. The mechanisms underlying -RPE signaling impairments in addiction may contribute to the disadvantageous nature of excessive drug use, which can persist despite repeated unfavorable life experiences (e.g., frequent incarcerations).
Somatostatin and its analogues bind to somatostatin receptors (sst) 1 through 5 that are overexpressed in neuroendocrine neoplasms such as gastroenteropancreatic (GEP) malignancies. After ...ligand-receptor binding, a fraction of the ligand-receptor complexes internalize. This internalization process is an effective means of delivering cytotoxic radiolabeled somatostatin analogues, especially those emitting short-range decay particles such as Auger electrons, to the neoplastic cell nucleus. Indium-111-pentetreotide, an sst 2 preferring somatostatin analogue with gamma and Auger electron decay characteristics, is commonly used for the scintigraphic evaluation and management of neuroendocrine cancer patients. This clinical trial was performed to determine the effectiveness and tolerability of therapeutic doses of
111In-pentetreotide in patients with GEP tumors. GEP tumor patients who had failed all forms of conventional therapy, with worsening of tumor-related signs and symptoms and/or radiographically documented progressive disease, an expected survival less than 6 months, and sst positivity as determined by the uptake on a 6.0 mCi
111In-pentetreotide scan (OctreoScan; Mallinckrodt Medical, Inc, St. Louis, MO), were treated with at least 2 monthly 180-mCi intravenous injections of
111In-pentetreotide. Baseline clinical assessments, serum chemistries, and plasma pancreastatin levels were measured and repeated before each
111In-pentetreotide treatment. From February 1997 to February 1998, 27 GEP (24 carcinoid neoplasms with carcinoid syndrome and 3 pancreatic islet cells) patients were accrued, with 26 patients evaluable for clinical and radiographic responses, 21 patients evaluable for biochemical assessments, and 27 patients evaluable for survival analysis and safety. Toxicity was evaluated by using standard National Cancer Institute (NCI) Common Toxicity Criteria guidelines. Clinical benefit occurred in 16 (62%) patients. Pancreastatin levels decreased by 50% or more in 81% of the patients. Objective partial radiographic responses occurred in 2 (8%) patients, and significant tumor necrosis (defined by 20 Hounsfield units or greater decrease from baseline) developed in 7 (27%) patients. The following transient Grades 3/4 NCl Common Toxicity Criteria side effects were observed, respectively: leukocyte: 1/1; platelets: 0/2; hemoglobin: 3/0; bilirubin: 1/3; creatinine: 1/0; neurologic: 1/0. Myeloproliferative disease and/or myelodysplastic syndrome have not been observed in the 6 patients followed-up for 48+ months. The median survival was 18 months (range, 3–54+ mo). Two doses (180 mCi) of
111In-pentetreotide are safe, well-tolerated, and improve symptoms in 62% of patients, decrease hormonal markers in 81% of patients, decrease Hounsfield units on computed tomography (CT) scans in 27% of patients, with 8% partial radiographic responses and increased expected survival in GEP cancer patients with somatostatin receptor-expressing tumors. The maximal tolerated dose of
111In-pentetreotide and the optimal dosing schedules remain under investigation.
Deficits in prefrontal cortical (PFC) function have been consistently reported in individuals with cocaine use disorders (iCUD), and have separately been shown to improve with longer‐term abstinence. ...However, it is less clear whether the PFC structural integrity possibly underlying these deficits is also modulated by sustained reduction in drug use in iCUD. Here, T1‐weighted magnetic resonance imaging scans were acquired, and performance on a neuropsychological test battery was assessed, in 19 initially abstinent treatment‐seeking iCUD, first at baseline and then after six months of significantly reduced or no drug use (follow‐up). A comparison cohort of 12 healthy controls was also scanned twice with a similar inter‐scan interval. The iCUD showed increased gray matter volume in the left inferior frontal gyrus and bilaterally in the ventromedial prefrontal cortex at follow‐up compared to baseline; healthy controls, as expected, showed no changes over this same time period. The iCUD also showed improved decision making and cognitive flexibility, with the latter correlated significantly with the gray matter volume increases in the inferior frontal gyrus. Given its association with improved cognitive function, the longitudinal recovery in cortical gray matter volume, particularly in regions where structure and function are adversely affected by chronic drug use, reflects a quantifiable positive impact of significantly reduced drug use on cortical structural integrity.
This study reports the longitudinal recovery in prefrontal cortical gray matter volume, particularly in regions that are adversely affected by chronic drug use, after 6months abstinence or reduction in cocaine use in treatment seeking individuals with chronic cocaine use. The study also reports longitudinal improvements in decision making and cognitive flexibility, with the latter correlated significantly with longitudinal increase in prefrontal gray matter volume. Results reflect a quantifiable positive impact of significantly reduced drug use on cortical structural integrity.
Limited data are available on the relative effect of drug-eluting versus bare-metal stents on the requirement for subsequent coronary artery bypass grafting (CABG). The aim of this study was to ...evaluate the incidence and predictors of CABG after bare-metal and paclitaxel-eluting coronary stent implantation. A patient-level, pooled analysis was conducted of 2,736 patients from 3 double-blind, randomized trials comparing the slow-release paclitaxel-eluting Taxus stent with an otherwise identical bare-metal stent control in single de novo coronary lesions, with 5-year follow-up. The rate of target lesion revascularization by CABG (TLR-CABG) was reduced from 4.1% in patients with bare-metal stents to 1.4% in those with Taxus stents (p <0.001). The use of the Taxus stent was the strongest predictor of freedom from TLR-CABG on multivariate analysis (hazard ratio 0.33, p <0.001). Significant reductions in TLR-CABG with Taxus compared with bare-metal stents were seen in the treatment of left anterior descending artery lesions (6.1% vs 1.8%, p <0.001) and non–left anterior descending artery lesions (2.8% vs 1.3%, p = 0.037), in patients with diabetes (6.0% vs 1.0%, p <0.01), and in those without diabetes (3.5% vs 1.6%, p <0.01). In conclusion, referral to CABG is significantly less common after stenting single coronary lesions with Taxus compared with bare-metal stents. The relative reductions in TLR-CABG of 54% in patients without diabetes, 87% in patients with diabetes, 70% in left anterior descending artery lesions, and 54% in non–left anterior descending artery lesions with Taxus compared with bare-metal stents should be considered during stent selection.
Additively manufactured methanol conversion reactor was designed and fabricated for high throughput fuel production while capturing carbon dioxide. The reactor designed is part of large effort in ...integrating electrolyzer and catalytic reactor system. Processing in fabricating the steel, titanium, and nickel alloy reactors were optimized to improve the catalyst deposition process and reaction efficiency. Microstructure of the additively manufactured reactors were characterized. General design is utilized to improve the performance of the reactor while exploring the benefit of freeform in additive manufacturing.
Additively manufactured methanol conversion reactor was designed and fabricated for high throughput fuel production while capturing carbon dioxide. Here, the reactor designed is part of large effort ...in integrating electrolyzer and catalytic reactor system. Processing in fabricating the steel, titanium, and nickel alloy reactors were optimized to improve the catalyst deposition process and reaction efficiency. Microstructure of the additively manufactured reactors were characterized. General design is utilized to improve the performance of the reactor while exploring the benefit of freeform in additive manufacturing.
Zero-cross and zero-derivative period amplitude analysis (PAA) data were compared with power spectral analysis (PSA) data obtained with the fast Fourier transform in all-night sleep EEG from 10 ...subjects. Although PAA zero-cross–integrated amplitude showed good agreement with PSA power in 0.3–2 Hz, zero-cross analysis appears relatively ineffective in measuring 2–4 Hz and above waves. However, PAA zero-derivative measures of peak-trough amplitude correlated well with PSA power in 2–4 Hz. Thus, while PAA appears able to measure the entire EEG spectrum, the analytic technique should be changed from zero cross to zero derivative at about 2 Hz in human sleep EEG. PAA and PSA both demonstrate robust and interrelated across-night oscillations in three frequency bands: delta (0.3–4 Hz); sigma (12–16 Hz); and fast beta (20–40 Hz). The frequencies between delta and sigma, and between sigma and fast beta, did not show clear across-night oscillations using either method, and the two methods showed lower epoch-to-epoch agreement in these intermediate bands. The causes of this reduced agreement are not immediately clear, nor is it obvious which method gives more valid results. We believe that the three strongly oscillating frequency bands represent fundamental properties of the human sleep EEG that provide important clues to underlying physiological mechanisms. These mechanisms are more likely to be understood if their dynamic properties are preserved and measured naturalistically rather than being forced into arbitrary sleep stages or procrustean models. Both PAA and PSA can be employed for such naturalistic studies. PSA has the advantages of applying the same analytic method across the EEG spectrum and rests on more fully developed theory. Combined zero-cross and zero-derivative PAA demonstrates EEG oscillations that closely parallel those observed with spectral power, and the PAA measures do not rely on assumptions about the spectral composition of the signal. In addition, both PAA techniques can measure the relative contributions of wave amplitude and incidence to total power. These waveform characteristics represent different biological processes and respond differentially to a wide range of experimental conditions.
PDF
