Search

The paper describes recent progress for the introduction of silicon-germanium, bipolar and field effect heterostructure transistors into mainstream integrated circuit application. Basic underlying concepts and device architectures which give rise to the desired performance advantages are described together with the latest state-of the-art results for HBT and MOSFET devices. The integration of such devices into viable HBT, BiCMOS and CMOS is reviewed. Other contributions that SiGe can make to enhance the performance of ULSI circuits are mentioned also.

A fluorescent derivative of GDP was prepared by the reaction of 2'-amino-2'-deoxy-GDP with fluorescamine. This derivative binds tightly (KD approximately 4.5 X 10(-8) M) to elongation factor Tu (EF-Tu) from Escherichia coli. The emission properties, including spectra, polarizations, and lifetimes, for fluorescamine-GDP free in solution and bound to EF-Tu are presented. Emission data on the fluorescamine-ethylamine conjugate are also given. A multifrequency phase and modulation lifetime study (using nine modulation frequencies over the range of 2-80 MHz) indicated that the emissions of these three systems were well characterized by single exponential decays corresponding to 1.45 ns for the fluorescamine-ethylamine derivative in buffer and to 7.74 and 11.03 ns for the fluorescamine-GDP derivative free in buffer and bound to EF-Tu, respectively. Multifrequency differential polarized phase fluorometry results indicated a rotational relaxation time of the protein-probe complex of approximately 88 ns; these data also indicated the lack of significant local motion for the probe. Addition of excess GDP to the EF-Tu-probe complex led to displacement of the fluorescamine-GDP derivative as evidenced by the change in both the steady-state and dynamic polarization values. The observed increase in fluorescence intensity upon displacement allowed us to follow the kinetics of the dissociation reaction; a dissociation rate constant of 5.0 X 10(-3) S-1 was determined. These results demonstrate the utility of this 2'-amino-2'-deoxy-GDP analogue as a probe of guanosine nucleotide dependent systems.

The intrinsic fluorescence properties of elongation factor Tu (EF-Tu) in its complexes with GDP and elongation factor Ts (EF-Ts) have been investigated. The emission spectra for both complexes are dominated by the tyrosine contribution upon excitation at 280 nm whereas excitation at 300 nm leads to exclusive emission from the single tryptophan residue (Trp-184) of EF-Tu. The fluorescence lifetime of this tryptophan residue in both complexes was investigated by using a multifrequency phase fluorometer which achieves a broad range of modulation frequencies utilizing the harmonic content of a mode-locked laser. These results indicated a heterogeneous emission with major components near 4.8 ns for both complexes. Quenching experiments on both complexes indicated limited accessibility of the tryptophan residue to acrylamide and virtually no accessibility to iodide ion. The quenching patterns exhibited by EF-Tu-GDP and EF-Tu X EF-Ts were, however, different; both quenchers were more efficient at quenching the emission from the EF-Tu x EF-Ts complex. Steady-state and dynamic polarization measurements revealed limited local mobility for the tryptophan in the EF-Tu x GDP complex whereas formation of the EF-Tu x EF-Ts complex led to a dramatic increase in this local mobility.

Dorsal root ganglia and sciatic nerve of the peripheral nervous sytem (PNS) were studied to examine the expression of platelet-derived growth factor (PDGF) and and PDGF alpha- and beta-receptors. High level expression of PDGF were detected in neonatal rat dorsal root ganglia and sciatic nerve. The receptors, on the other hand, were highly expressed in neonatal rat PNS. The findings indicate that PDGF play a role in the development of the PNS and in maintenance of peripheral neurons.

AIM OF REPORT. This report reviews the evidence about the effectiveness of treatments for chronic pain. While treatment of chronic pain is usually seen as an integrated service, this report concentrates on the individual interventions that constitute the service. HOW THE RESEARCH WAS CONDUCTED. Searches of databases and journals identified over 15,000 randomised studies with pain as an outcome, and many more which were not randomised. Over 150 systematic reviews relevant to chronic pain treatment were identified and their quality assessed using a simple scoring system. Systematic reviews conducted for this report were based mainly on randomised trials. The number needed to treat (NNT) was chosen as the output for the report. NNTs of 2-4 indicate effective treatments. Because NNT is treatment-specific it overcomes problems associated with highly variable placebo or control event rates in pain trials. Such variability is predominantly due to the limited numbers of patients in the clinical trials. Dichotomous outcome measures are important in synthesising information from many studies, and in deriving NNTs. Methods have been developed which allow mean information on pain relief and intensity to be converted reliably into the simple dichotomous outcome of at least 50% pain relief. RESEARCH FINDINGS. PHYSICAL INTERVENTIONS. Transcutaneous electrical nerve stimulation (TENS) has been shown not to be effective in postoperative and labour pain. In chronic pain, there is evidence that TENS effectiveness increases slowly, and that large doses need to be used. There is lack of evidence for the effectiveness of TENS in chronic pain. There is a lack of evidence for the effectiveness of relaxation. Intravenous systemic regional blockade with guanethidine has been shown to be without effect. Epidural corticosteroids are effective in the short term for back pain and sciatica. Injections of corticosteroids in or around shoulder joints for shoulder pain have been shown not to be effective. There is a lack of evidence supporting spinal cord stimulators. Case series are of poor quality and do not provide evidence of effectiveness, although at least 50% pain relief at 5 years is reported in over 50% of patients. PHARMACOLOGICAL INTERVENTIONS. Minor analgesics are important in chronic pain. NNTs were calculated for analgesics given orally for moderate or severe acute postoperative pain. The NNTs found ranged from 17 (poor) for codeine, 60 mg, to 2.5 (good) for ibuprofen, 400 mg. Anticonvulsant and antidepressant drugs are prescribed for neuropathic pains like diabetic neuropathy. NNTs are of the order of 2.5, showing them to be effective treatments. However, there are too few studies with too few patients to determine which is the best drug. Minor adverse events are common, and major adverse events occur in about 1 in 20 patients. There are no studies comparing antidepressants and anticonvulsants directly. Systemic local anaesthetic-type drugs have been shown to be effective in nerve injury pain but there is little or no evidence to support their use in migraine or cancer-related pain. Topical NSAIDs (for example, gels, creams) are effective in rheumatological conditions with an overall NNT of 3. There are too few studies to determine which is the best agent. Topical NSAIDs have few adverse events; most importantly they are without the major gastrointestinal adverse events found with oral NSAIDs, which might make them an important choice for some patients with peripheral arthritis. (ABSTRACT TRUNCATED)

Background: National cardiac registries are increasingly used for informing health policy, improving the quality and cost-effectiveness of patient care, clinical research, and monitoring the safety of novel treatments. However, the quality of registries is variable. We aimed to assess the characteristics and quality of national cardiac registries across all subspecialties of cardiac care.Methods: Publications relating to national cardiac registries across six cardiac subspecialty domains were identified by searching MEDLINE and the Google advanced search function with 26 438 citations and 4812 full-text articles reviewed.Results: A total of 155 registries, representing 49 countries, were included in the study. Of these, 45 related to coronary disease or percutaneous coronary intervention, 28 related to devices, arrhythmia, and electrophysiology, 24 related to heart failure, transplant, and mechanical support, 21 related to structural heart disease, 21 related to congenital heart disease, and 16 related to cardiac surgery. Enrollment was procedure-based in 60% and disease-based in 40%. A total of 73.10 million patients were estimated to have been enrolled in cardiac registries. Quality scoring was performed using a validated registry grading system, with registries performing best in the use of explicit variable definitions and worst in assessment of data reliability. Higher quality scores were associated with government funding, mandated enrollment, linkage to other registries, and outcome risk adjustment. Quality scores and number of registries within a country were positively correlated with each other and with measures of national economic output, health expenditure, and urbanization.Conclusions: There has been remarkable growth in the uptake of national cardiac registries across the last few decades. However, the quality of processes used to ensure data completeness and accuracy remain variable and few countries have integrated registries covering multiple subspecialty domains. Clinicians, funders, and health policymakers should be encouraged to focus on the range, quality, and integration of these registries. Registration: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020204224. [ABSTRACT FROM AUTHOR]

Introduction: Amlodipine overdoses have significant cardiac toxicity and are difficult to treat. Methylene blue has potential as a treatment for overdoses.Methods: A randomized controlled study of methylene blue as a treatment for amlodipine toxicity was conducted in C57Bl/6 mice. A baseline echocardiography was followed by gavage administration of amlodipine (90 mg/kg). Five minutes after gavage, animals received either vehicle solution (controls) or methylene blue (20 mg/kg) by intra-peritoneal injection. Animals were continuously monitored, and cardiac parameters were acquired every 15 min up to two hours.Results: Only 50% of control animals survived to the two-hour endpoint compared to 83% that received methylene blue. Amlodipine delivery induced significant reduction in left ventricular ejection fraction (EF), fractional shortening (FS), stroke volume (SV), and cardiac output (CO) in the vehicle treated animals relative to animals in the treatment group (p < 0.05 vehicle versus Methylene blue for EF, FS, SV, CO, and HR).Discussion: The amlodipine dose induced cardiotoxicity that were effects were more pronounced in the untreated group. 50% vehicle controls quickly progressed into heart failure (within 90 min of exposure) and did not survive the two h observation endpoint. Distinctly, only one animal from the Methylene blue treatment group did not survive (83% survival) the study. Additionally, the surviving animals from the Methylene blue group displayed significantly higher ejection fraction, fractional shortening, stroke volume, and cardiac output compared to vehicle group, indicating that methylene blue preserved cardiac function.Conclusion: In this mouse model of amlodipine overdose, methylene blue decreased cardiac toxicity. [ABSTRACT FROM AUTHOR]

Abstract Genetic models partitioning additive and non-additive genetic effects for populations tested in replicated multi-environment trials (METs) in a plant breeding program have recently been presented in the literature. For these data, the variance model involves the direct product of a large numerator relationship matrix A, and a complex structure for the genotype by environment interaction effects, generally of a factor analytic (FA) form. With MET data, we expect a high correlation in genotype rankings between environments, leading to non-positive definite covariance matrices. Estimation methods for reduced rank models have been derived for the FA formulation with independent genotypes, and we employ these estimation methods for the more complex case involving the numerator relationship matrix. We examine the performance of differing genetic models for MET data with an embedded pedigree structure, and consider the magnitude of the non-additive variance. The capacity of existing software packages to fit these complex models is largely due to the use of the sparse matrix methodology and the average information algorithm. Here, we present an extension to the standard formulation necessary for estimation with a factor analytic structure across multiple environments.