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[Patient autonomy].

Respecting the patient's autonomy is one of the fundamental principles on which biomedical ethics is based. The principle of autonomy considers the patient's freedom and responsibility, who decides what is good for himself/herself, although this is not shared by the physician. In the field of medical research, there are codes and guidelines that guarantee the protection of persons as research subjects. In Spain, recognition of the right of the patient's autonomy has been included in different legal and deontological guidelines. Law of Patient's Autonomy 41/2002 (LAP) is a response to the growing important in our society of the patients' rights as basic axis of the clinical-health care relationships. Different regional communities have also enacted legal guidelines that regulate the persons' autonomy to decide about that affecting his/her health, physical integrity, or life as well as the assumption by others of the decisions of representation or previous instructions. The basic paradigm of autonomy is the informed consent. The LAP establishes the obligation of obtaining the free and voluntary consent of the patient prior to any type of intervention, after offering him/her the adequate information. This basic guideline specifies the situations in which the informed consent is given in writing as well as the exceptions to this consent. Finally, the LAP details when the informed consent is advisable by representation, closely linked to the patient's capacity as well as the regulation of previous instructions.

Ethics, Medical↗

Perceptual strategies of isolation in obsessive-compulsive personality disorder.

Recent findings have shown that the Defense Mechanism Test, a serial tachistoscopic technique developed inside the percept-genetic frame of reference, discriminates neurotics from normals, neurotics from schizophrenic outpatients, and subjects with histrionic personality disorder from controls. The present research addresses another major class of Axis II pathology, comparing on the Defense Mechanism Test a group with a psychometric diagnosis of obsessive-compulsive personality disorder (n = 26) with a matched sample of noncompulsive controls. As predicted, several variants of isolation were significantly more characteristic of the compulsive group. Intellectualization, disappearance of the whole structure, whitening of the hero, and lack of recognition of the threat were the variants of isolation with the best discriminative properties. Codings of reaction formation were not linked with compulsive personality, which is congruent with the recent observation of their correspondence to the histrionic personality disorder. The findings are presented in the context of the percept-genetic literature on obsessive-compulsive defensive strategies.

Adult↗

Guidelines for dispensing medications.

Federal and state codes exist regarding administering and dispensing medications and there is variation between the two. Recognition of the differences is imperative for the athletic trainer, who has traditionally dispensed these agents in compliance with established legal and professional guidelines. Statutes that apply to classifying, documenting, prescribing, dispensing, labeling, and housing medications by athletic trainers are presented as a baseline for this article. State and local regulations should be consulted to clarify differences existing at various governmental levels. These guidelines are provided to assist athletic trainers in properly dispensing medications.

Journal Article↗

Recent developments with the nucleus 22-electrode cochlear implant: a new two formant speech coding strategy and its performance in background noise.

A clinical evaluation of speech processing strategies for the Nucleus 22-electrode cochlear implant showed improvements in understanding speech using the new FOF1F2 speech coding strategy instead of the F0F2 strategy. Significant improvement in closed-set speech recognition in the presence of background noise was an additional advantage of the new speech processing strategy.

Cochlear Implants↗

Speech perception abilities of adult and pediatric Nucleus implant recipients using the Spectral Peak (SPEAK) coding strategy.

A series of 73 postlinguistically deafened adults and 34 prelinguistically deafened children were evaluated with the Spectral Peak (SPEAK) coding strategy of the Nucleus 22-channel cochlear implant. The adults who received consecutive implants demonstrated rapid acquisition of open-set speech recognition skills in the initial postoperative period. Group mean sentence recognition improved to 53.5% (n = 52) after 2 weeks, 62.1% (n = 55) after 1 month, 69.8% (n = 57) after 3 months, and 74.4% (n = 42) after 6 months of use. At the 6-month evaluation interval, 43% of subjects scored greater than 90% on sound-alone sentence recognition in quiet and only one patient (2.4%) scored less than 10%. Mean monosyllabic word recognition was 35.6% after 6 months of use. The 34 prelinguistically deafened children were converted from the Multipeak strategy to Spectral Peak strategy at four large pediatric implant centers. After 6 months of using the new coding strategy, the children demonstrated significant improvements in their speech perception abilities.

Adult↗

Creating new restriction sites by silent changes in coding sequences.

We present methods for identifying a useful type of DNA site--one that can be mutated to create a new restriction site within a coding region without changing the amino acid sequence. These "latent sites" are abundant--silent mutations creating one of 44 different 6-bp or 8-bp recognition sites were found at relatively high density, roughly one latent site per 9 bp, in the eleven genes tested. Our analysis suggests that site-directed mutagenesis can be used to refashion coding sequences at will for flexible analysis.

Base Sequence↗

Sequence context effects on oligo(dT) termination signal recognition by Saccharomyces cerevisiae RNA polymerase III.

Eukaryotic RNA polymerase (Pol) III terminates transcription at short runs of T residues in the coding DNA strand. By genomic analysis, we found that T(5) and T(4) are the shortest Pol III termination signals in yeasts and mammals, respectively, and that, at variance with yeast, oligo(dT) terminators longer than T(5) are very rare in mammals. In Saccharomyces cerevisiae, the strength of T(5) as a terminator was found to be largely influenced by both the upstream and the downstream sequence context. In particular, the CT sequence, which is naturally present downstream of T(5) in the 3'-flank of some tDNAs, was found to act as a terminator-weakening element that facilitates translocation by reducing Pol III pausing at T(5). In contrast, tDNA transcription termination was highly efficient when T(5) was followed by an A or G residue. Surprisingly, however, when a termination-proficient T(5) signal was taken out from the tDNA context and placed downstream of a fragment of the SCR1 gene, its termination activity was compromised, both in vitro and in vivo. Even the T(6) sequence, acting as a strong terminator in tRNA gene contexts, was unexpectedly weak within the SNR52 transcription unit, where it naturally occurs. The observed sequence context effects reflect intrinsic recognition properties of Pol III, because they were still observed in a simplified in vitro transcription system only consisting of purified RNA polymerase and template DNA. Our findings strengthen the notion that termination signal recognition by Pol III is influenced in a complex way by the region surrounding the T cluster and suggest that read-through transcription beyond T clusters might play a significant role in the biogenesis of class III gene products.

Animals↗

An operational RNA code for amino acids and possible relationship to genetic code.

RNA helical oligonucleotides that recapitulate the acceptor stems of transfer RNAs, and that are devoid of the anticodon trinucleotides of the genetic code, are aminoacylated by aminoacyl tRNA synthetases. The specificity of aminoacylation is sequence dependent, and both specificity and efficiency are generally determined by only a few nucleotides proximal to the amino acid attachment site. This sequence/structure-dependent aminoacylation of RNA oligonucleotides constitutes an operational RNA code for amino acids. To a rough approximation, members of the two different classes of tRNA synthetases are, like tRNAs, organized into two major domains. The class-defining conserved domain containing the active site incorporates determinants for recognition of RNA mini-helix substrates. This domain may reflect the primordial synthetase, which was needed for expression of the operational RNA code. The second synthetase domain, which generally is less or not conserved, provides for interactions with the second domain of tRNA, which incorporates the anticodon. The emergence of the genetic from the operational RNA code could occur when the second domain of synthetases was added with the anticodon-containing domain of tRNAs.

Amino Acid Sequence↗

The signal recognition particle receptor alpha subunit of the hyperthermophilic archaeon Acidianus ambivalens exhibits an intrinsic GTP-hydrolyzing activity.

Two adjacent genes of the acidophilic and hyperthermophilic crenarchaeon Acidianus ambivalens were cloned and sequenced. The 1.6 kb genomic nucleotide sequence under investigation consists of the 1.12 kb SRa gene encoding the putative signal recognition particle receptor alpha subunit (SR alpha, 42.2 kDa) and the 186 basepair secE gene coding for the putative secretory component secE subunit (6800 Da). The SR alpha protein is structured by three distinct regions: the N-terminal hydrophilic H-region, the following X-region and the C-terminal GTP-binding domain. A polyclonal anti-E. coli lacZ/A. ambivalens SR alpha antiserum detects a 51 kDa cell protein (p51) on immunoblots. Proteolysis of the recombinant SR alpha protein by Proteinase K produces a 31.6 kDa protease-resistant protein fragment comprising X-region and G-domain. The protein binds tightly to the GTP-agarose affinity matrix in a temperature-dependent manner. It hydrolyzes GTP readily at higher temperatures only in the presence of Mg2+. Point mutations (T326N) and (D329A) in the G-4 element of A. ambivalens SR alpha G-domain diminish the GTPase activity significantly. In contrast, the deletion mutant protein SR alpha (delta1-92) lacking the hydrophilic H-region displays a higher GTP-hydrolyzing activity when compared to the unmodified recombinant protein. Addition of GDP greatly inhibits GTP hydrolysis in mutant and unmodified A. ambivalens SR alpha.

Amino Acid Sequence↗

Internal structure of the silk fibroin gene of Bombyx mori. I The fibroin gene consists of a homogeneous alternating array of repetitious crystalline and amorphous coding sequences.

The DNA sequence orgainzation of the protein encoding region of the gene for silk fibroin has been analyzed. The accompanying paper (Manningm R. F., and Gage, L. P. (1980) J. Biol. Chem. 255, 9451-9457) shows that the total length of the gene, and its protein, as well as the pattern of restriction sites in the gene is highly polymorphic among inbred stocks of Bombyx mori, In this paper, those features of fibroin gene structure which are invariant among these alleles are presented. Fibroin is composed primarily of relatively short "crystalline" and "amorphous" peptides of known sequence whose arrangement in the protein is unknown. Knowledge of the codons most commonly used in fibroin mRNA allowed utilization of particular restriction inzymes as a means for determing the nature and organization of crystalline and amorphous coding sequences in the fibroin gene. Three restriction endonucleases were identified that cleve sequences coding for amorphous region peptides. Their cleavage pattern revelaed that the repetitive coding sequence of the gene core (approximately 15 kilobases) is divided into at least 10 large crystalline coding domains interrupted by smaller amorphous coding domains. Many restriction endoncleases do not cleave the fibroin core at all, three of them with four gase recognition sequences. Specific deductions as to codon usage and repetitive sequence homogeneity in the gene follow from these results. One novel finding is the rigorous exclusion of the glycine codon GGA prior to serine codons even though this glycine codon is used frequently prior to alanine codons. The sequence homogeneity and the regularly alternating arrangement of crystalline and amorphous coding sequences of the gene are discussed in terms of the function of fibroin protein and the evolution of highly repetitive DNA.

Alleles↗

Detection of Kanji words in a rapid serial visual presentation task.

In 3 experiments, lists of 12 Kanji words were rapidly presented in the same position, and participants reported a red target word embedded in green distractor words. Two lists were used: same and different category. A tendency toward category priming was found at longer durations. Frequency of target localization indicated that participants familiar with Kanji had a greater tendency to report the word immediately preceding the target. These pretarget intrusion errors dominated the posttarget intrusion errors, when the luminance of red and green stimuli were equated (Experiment 2), and when the response was recall (Experiments 1 and 2) or recognition (Experiment 3). In contrast, participants unfamiliar with Kanji made posttarget intrusion errors as frequently as pretarget intrusion errors (Experiment 3), suggesting that knowledge of Kanji influences the integration of color and form codes in visual information processing.

Adult↗

Reinitiation of a lac repressor fragment at a codon other than AUG.

52 Spontaneous nonsense mutants in the lac i gene of Escherichia coli were isolated and characterized. All mutants located early in the gene show negative complementation in vivo with a wild-type i gene in a recA diploid strain. In vitro studies show that those mutants that display negative complementing activity in vivo also make lac repressor fragments retaining inducer binding and immunological crossreactivity with wild-type repressor. Amino-acid sequence analysis of these fragments shows that they arise by reinitiation at internal sities of the i message after chain termination at a prior amber or ochre codon. There are at least two different internal reinitiation sites in the first 200 nucleotides of the translated part of the i message. The first site corresponds to the first internal in phase AUG codon, which specifies the methionine residue at position 42 of the repressor protein. This site can be activated by an amber codon, 45 nucleotides before the AUG codon. The second site is only 60 nucleotides past the first site and can be activated by an amber mutation derived from residue 60 of the protein. The second initiation codon specifies the amino-acid leucine in the wild-type repressor, but the reinitiated fragment shows an amino-terminal methionine residue at this position. Therefore, the second initiation site seems to involve an in vivo ambiguity of the genetic code in that the same codon can be translated into two different amino acids depending on the recognition of this codon during initiation (when methionine is inserted) or elongation of protein synthesis (when leucine is inserted). The possibility that a codon other than AUG can act as an initiation codon in vivo is discussed.

Adenine Nucleotides↗

Regulation of rat glutathione S-transferase Ya subunit gene expression. DNA-protein interaction at the antioxidant responsive element.

We have characterized the interaction of the antioxidant responsive element (ARE) in the 5'-flanking region of the rat glutathione S-transferase Ya subunit gene with its trans-acting factor. The ARE core sequence, 5'-ggTGACaaaGC-3', previously identified as the cis-acting element required for activation of the Ya subunit gene by planar aromatic compounds and phenolic antioxidants, is shown to be the high affinity recognition motif for a trans-acting factor(s) as determined by gel mobility shift assays as well as methylation interference and protection studies. The DNA-protein interaction appears to occur in the major groove and involves the GpG dinucleotide preceding and the G residue within the TGAC tetramer on the coding strand of the core sequence. In addition, DNase I protection analysis maps an extended region 5' from the core recognition motif, which was shown previously to be essential for basal activity of the ARE. The trans-acting factor is present in nuclear extracts from untreated and tert-butylhydroquinone-treated cells as determined by photochemical cross-linking experiments. The cross-linked protein appears to be a heterodimer with subunit molecular weights of approximately 28,000 and approximately 45,000.

Animals↗

Behavioral or hemispheric asymmetry: is there a default option?

The presence of acuity gradients as a moderating variable in hemifield research is not in question. Their importance as a determinant of hemifield differences is unclear, however. The major issues are as follows. First, do vertical displays provide an appropriate control for the acuity gradient? Second, do the initial letters of a word play a critical role in word recognition, either in information-theoretic terms or because the lexicon is itself organized around access codes based on the initial letter or letters of words? Third, do behavioral and hemispheric accounts provide equally attractive explanations of Task Level X Visual Field interactions? Fourth, if the two accounts are equally attractive on empirical grounds, which is to be preferred? Each of these issues is addressed in this reply to M. P. Bryden's (1986, Brain and Cognition, 5, 362-368) and J. Hellige's (1986, Brain and Cognition, 5, 369-376) comments on our article (K. Kirsner & S. Schwartz 1986, Brain and Cognition, 5, 354-361).

Brain↗

Evolutionary optimization of a hierarchical object recognition model.

A major problem in designing artificial neural networks is the proper choice of the network architecture. Especially for vision networks classifying three-dimensional (3-D) objects this problem is very challenging, as these networks are necessarily large and therefore the search space for defining the needed networks is of a very high dimensionality. This strongly increases the chances of obtaining only suboptimal structures from standard optimization algorithms. We tackle this problem in two ways. First, we use biologically inspired hierarchical vision models to narrow the space of possible architectures and to reduce the dimensionality of the search space. Second, we employ evolutionary optimization techniques to determine optimal features and nonlinearities of the visual hierarchy. Here, we especially focus on higher order complex features in higher hierarchical stages. We compare two different approaches to perform an evolutionary optimization of these features. In the first setting, we directly code the features into the genome. In the second setting, in analogy to an ontogenetical development process, we suggest the new method of an indirect coding of the features via an unsupervised learning process, which is embedded into the evolutionary optimization. In both cases the processing nonlinearities are encoded directly into the genome and are thus subject to optimization. The fitness of the individuals for the evolutionary selection process is computed by measuring the network classification performance on a benchmark image database. Here, we use a nearest-neighbor classification approach, based on the hierarchical feature output. We compare the found solutions with respect to their ability to generalize. We differentiate between a first- and a second-order generalization. The first-order generalization denotes how well the vision system, after evolutionary optimization of the features and nonlinearities using a database A, can classify previously unseen test views of objects from this database A. As second-order generalization, we denote the ability of the vision system to perform classification on a database B using the features and nonlinearities optimized on database A. We show that the direct feature coding approach leads to networks with a better first-order generalization, whereas the second-order generalization is on an equally high level for both direct and indirect coding. We also compare the second-order generalization results with other state-of-the-art recognition systems and show that both approaches lead to optimized recognition systems, which are highly competitive with recent recognition algorithms.

Algorithms↗