Abstract Objective This double-blind study compared a second generation (atypical) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid ...illicit substances. Methods Schizophrenic subjects were recruited at 57 U.S. sites and randomly assigned to olanzapine, perphenazine, quetiapine, risperidone or ziprasidone for up to 18 months. The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances. Results There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs (median 3.3 to 6.8 months). Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine (median 13.0 months) than perphenazine ( 5.9 months), risperidone (5.6 months), or quetiapine (5.0 months); time to discontinuation for ziprasidone (4.3 months) was even shorter, although the latter difference was not significant. The difference between risperidone and quetiapine, although small, was significant. All remaining differences were non-significant. Similar results were found for discontinuation due to inefficacy. There were no differences between illicit users and non-users in symptom reduction and global improvement, after adjustment for differential duration of treatment. Differences in discontinuation results were attenuated by non-compliance, but the trends persisted after controlling for treatment compliance. Conclusions Among patients with chronic schizophrenia who avoid use of illicit drugs, olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation, but illicit substance abuse attenuated this advantage, reinforcing the need for concurrent substance abuse treatment.
Caldesmon (CaD) is a major actin-binding protein distributed in a variety of cell types. No functional differences among the isoforms in in vitro studies were found so far. In a previous study we ...found that the low molecular caldesmon isoform (Hela l-CaD) is expressed in endothelial cells (ECs)/endothelial progenitor cells (EPCs) in tumor vasculature of various human tumors. Activation of cell motility is necessary for the navigation of the tip ECs during angiogenesis, and migration of EPCs from the bone marrow during vasculogenesis. In the present study we searched for features of motility and the intracellular expression sites of Hela l-CaD in ECs/EPCs of various human tumors under histologically preserved microenviroment. We discovered a variety of motility-related cell protrusions like filopodia, microspikes, lamellipodia, podosomes, membrane blebs and membrane ruffles in the activated ECs/EPCs. Hela l-CaD appeared to be invariably expressed in the subregions of these cell protrusions. The findings suggest that Hela l-CaD is implicated in the migration of ECs/EPC in human neoplasms where they contribute to tumor vasculogenesis and angiogenesis.
In the Noisy Intermediate Scale Quantum (NISQ) era, finding implementations of quantum algorithms that minimize the number of expensive and error prone multi-qubit gates is vital to ensure ...computations produce meaningful outputs. Unitary synthesis, the process of finding a quantum circuit that implements some target unitary matrix, is able to solve this problem optimally in many cases. However, current bottom-up unitary synthesis algorithms are limited by their exponentially growing run times. We show how applying machine learning to unitary datasets permits drastic speedups for synthesis algorithms. This paper presents QSeed, a seeded synthesis algorithm that employs a learned model to quickly propose resource efficient circuit implementations of unitaries. QSeed maintains low gate counts and offers a speedup of \(3.7\times\) in synthesis time over the state of the art for a 64 qubit modular exponentiation circuit, a core component in Shor's factoring algorithm. QSeed's performance improvements also generalize to families of circuits not seen during the training process.
Environmental risk limits (ERLs) for individual congeners of polychlorinated biphenyls (PCB 77, 105, 118, 126, 153, 156, 157, and 169) are derived. After lipid normalization, toxicity data for birds, ...mammals, and aquatic organisms were converted to equivalent concentrations in soil or sediment organic carbon (OC). Accumulation in the food chain was taken into account. Field‐derived data on the environmental fate of PCBs, e.g., biomagnification factors and biota‐to‐sediment accumulation factors, were used in the calculations. The variability in these data was incorporated by using probabilistic techniques. Parameters that are difficult to measure for these hydrophobic compounds, such as the bioconcentration factor or the sediment/water partition coefficient, were avoided where possible. Probability distributions for various species were combined per congener when statistically appropriate; ERLs were based on the fifth percentile of these combined distributions. Congener patterns occurring in various sediments and invertebrates in The Netherlands were used for determining a mixture ERL for non‐ and mono‐ortho PCBs. The PCB 118 was selected as a guiding congener. If the concentration of PCB 118 is less than 5 μg/kg OC, Dutch ecosystems are assumed to be protected for effects of the whole mixture of non‐ and mono‐ortho‐substituted PCBs. Concentrations associated with adverse effects in field studies were comparable to concentrations that would result if all congeners would be present at the ERL level.
Caldesmon (CaD) is a major actin-binding protein distributed in a variety of cell types. So far no diversity in functions of the different isoforms were found in in vitro studies. The low molecular ...weight isoform (Hela /-CaD) was detected in the vasculature of a variety of tumor types in our previous study. Proliferation of endothelial cells/endothelial progenitor cells (ECs/EPCs) is a crucial event for formation of new blood vessels. Here we report the intranuclear translocation of Hela /-CaD in cell cycle activated ECs/EPCs in the vasculature of human tumors. The nuclear translocation coincides with phosphorylation of the molecule and the activation of intranuclear protein kinase p34(cdc2). These findings point to a function of this molecule relating to DNA synthesis which is triggered by cell-cycle signalling pathways. The data challenge and update the generally accepted concept that CaD is a pure cytoplasmic protein in vitro study. It suggests that nuclear translocation of Hela /-CaD serves as an additional regulatory step in the control of mitotic initiation and triggers further investigations in the role of this protein in the regulation of nuclear investigations in the role of this protein in the regulation of nuclear functions.
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