Taming combinatorial explosion.
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Biological Evolution↗
Biomedical subjects
P Schuster
Publications and source records attributed to P Schuster.
Galileo at Io: results from high-resolution imaging.
During late 1999/early 2000, the solid state imaging experiment on the Galileo spacecraft returned more than 100 high-resolution (5 to 500 meters per pixel) images of volcanically active Io. We observed an active lava lake, an active curtain of lava, active lava flows, calderas, mountains, plateaus, and plains. Several of the sulfur dioxide-rich plumes are erupting from distal flows, rather than from the source of silicate lava (caldera or fissure, often with red pyroclastic deposits). Most of the active flows in equatorial regions are being emplaced slowly beneath insulated crust, but rapidly emplaced channelized flows are also found at all latitudes. There is no evidence for high-viscosity lava, but some bright flows may consist of sulfur rather than mafic silicates. The mountains, plateaus, and calderas are strongly influenced by tectonics and gravitational collapse. Sapping channels and scarps suggest that many portions of the upper approximately 1 kilometer are rich in volatiles.
Extraterrestrial Environment↗
Dynamics of autocatalytic replicator networks based on higher-order ligation reactions.
A class of autocatalytic reaction networks based on template-dependent ligation and higher-order catalysis is analysed. Apart from an irreversible ligation reaction we consider only reversible aggregation steps that provide a realistic description of molecular recognition. The overall dynamics can be understood by means of replicator equations with highly non-linear interaction functions. The dynamics depends crucially on the total concentration c0 of replicating material. For small c0, in the hyperbolic growth regime, we recover the familiar dynamics of second-order replicator equations with its wealth of complex dynamics ranging from multi-stability to periodic and strange attractors as well as to heteroclinic orbits. For large c0, in the parabolic growth regime, product inhibition becomes dominating and we observe a single globally stable equilibrium tantamount to permanent coexistence. In an intermediate parameter range we sometimes observe a behavior that is reminiscent of 'survival of the fittest'. Independently replicating species (Schlögl's model) and the hypercycle are discussed in detail.
Catalysis↗
RNA folding at elementary step resolution.
We study the stochastic folding kinetics of RNA sequences into secondary structures with a new algorithm based on the formation, dissociation, and the shifting of individual base pairs. We discuss folding mechanisms and the correlation between the barrier structure of the conformational landscape and the folding kinetics for a number of examples based on artificial and natural sequences, including the influence of base modification in tRNAs.
Algorithms↗
Complete suboptimal folding of RNA and the stability of secondary structures.
An algorithm is presented for generating rigorously all suboptimal secondary structures between the minimum free energy and an arbitrary upper limit. The algorithm is particularly fast in the vicinity of the minimum free energy. This enables the efficient approximation of statistical quantities, such as the partition function or measures for structural diversity. The density of states at low energies and its associated structures are crucial in assessing from a thermodynamic point of view how well-defined the ground state is. We demonstrate this by exploring the role of base modification in tRNA secondary structures, both at the level of individual sequences from Escherichia coli and by comparing artificially generated ensembles of modified and unmodified sequences with the same tRNA structure. The two major conclusions are that (1) base modification considerably sharpens the definition of the ground state structure by constraining energetically adjacent structures to be similar to the ground state, and (2) sequences whose ground state structure is thermodynamically well defined show a significant tendency to buffer single point mutations. This can have evolutionary implications, since selection pressure to improve the definition of ground states with biological function may result in increased neutrality.
Base Sequence↗
Force field based conformational analysis of RNA structural motifs: GNRA tetraloops and their pyrimidine relatives.
The protocol of conformational analysis applied here to ribonucleotide oligomers combines conformational search in the space of torsion angles and energy minimization using the AMBER4.1 force field with a continuum treatment of electrostatic solute-solvent interactions. RNA fragments with 5'-GGGCGNNAGCCU-3' sequences commonly fold into hairpins with four-membered loops. The combinatorial search for acceptable conformations using the MC-SYM program was restricted to loop nucleotides and yielded roughly 1500 structures being compatible with a double-stranded stem. After energy minimization by the JUMNA program (without applying any experimental constraints), these structures converged into an ensemble of 74 different conformers including 26 structures which contained the sheared G-A base pair observed in experimental studies of GNRA tetraloops. Energetic analysis shows that inclusion of solvent electrostatic effects is critically important for the selection of conformers that agree with experimentally determined structures. The continuum model accounts for solvent polarization by means of the electrostatic reaction field. In the case of GNRA loop sequences, the contributions of the reaction field shift relative stabilities towards conformations showing most of the structural features derived from NMR studies. The agreement of computed conformations with the experimental structures of GAAA, GCAA, and GAGA tetraloops suggests that the continuum treatment of the solvent represents a definitive improvement over methods using simple damping models in electrostatic energy calculations. Application of the procedure described here to the evaluation of the relative stabilities of conformers resulting from searching the conformational space of RNA structural motifs provides some progress in (non-homology based) RNA 3D-structure prediction.
Base Sequence↗
Prevalence, 20-month incidence and outcome of unipolar depressive disorders in a community sample of adolescents.
BACKGROUND: This article presents prospective longitudinal findings on prevalence, incidence, patterns of change and stability of depressive disorders in a community sample of 1228 adolescents. METHODS: Data were collected at baseline and follow-up (20 months later) in a representative population sample of 1228 adolescents, aged 14-17 at baseline. Diagnostic assessment was based on the Munich Composite International Diagnostic Interview (M-CIDI). RESULTS: The overall cumulative lifetime incidence of any depressive condition was 20.0% (major depressive disorder (MDD), 12.2%; dysthymia, 3-5%; subthreshold MDD, 6.3%), of which about one-third were incident depressions in the period between baseline and follow-up. Depressive disorders rarely started before the age of 13. Females were about twice as likely as males to develop a depressive disorder. Overall, the 20-month outcome of baseline depression was unfavourable. Dysthymia had the poorest outcome of all, with a complete remission rate of only 33% versus 43% for MDD and 54% for subthreshold MDD. Dysthymia also had the highest number of depressive episodes, and most psychosocial impairment and suicidal behavioural during follow-up. Treatment rates were low (8-23%). Subthreshold MDD associated with considerable impairment had an almost identical course and outcome as threshold MDD. CONCLUSIONS: DSM-IV MDD and dysthymia are rare before the age of 13, but frequent during adolescence, with an estimated lifetime cumulative incidence of 14%. Only a minority of these disorders in adolescence is treated, and more than half of them persist or remit only partly.
Adolescent↗
An update on safety studies of SAD B19 rabies virus vaccine in target and non-target species.
SAD B19 is an attenuated vaccine virus for oral vaccination of carnivores against rabies. The safety of SAD B19 was investigated in 16 animal species by different routes of administration. During the observation period all animals given the vaccine virus, irrespective of the route of administration, did not show any clinical signs of rabies, with the exception of certain rodent species. In these animals a low residual pathogenicity was observed, however transmission of the vaccine virus to control animals was not demonstrable. No vaccine virus could be detected in the saliva of the six mammal species examined. Furthermore, the genetical stability was shown for SAD B19 through passaging in neural tissue of dogs, foxes and mice. From the results presented here on innocuity and stability, it can be concluded that SAD B19 rabies vaccine is suitable for oral vaccination campaigns for carnivores against rabies.
Administration, Oral↗
Patterns of cannabis use, abuse and dependence over time: incidence, progression and stability in a sample of 1228 adolescents.
AIMS: To present data on the incidence of cannabis use at follow-up, and its progression, stability, abuse and dependence in a representative sample of adolescents (N = 1228), aged 14-17 years at "baseline"--the outset of the study--in Munich, Germany. DESIGN: The study employed a prospective longitudinal design using a representative population sample. The mean follow-up time was 19.7 months. The Composite International Diagnostic Interview (M-CIDI) was used to assess patterns of use, abuse and dependence according to DSM-IV criteria. FINDINGS: (1) In our sample, 34.8% of males and 30.2% of females had tried cannabinoids at least once. (2) Of those who used cannabis repeatedly (two or four times) at baseline, 26.1% stopped using by follow-up; the majority went on to regular use in the follow-up period. Similarly, only 17.7% of the regular users at the outset stopped using cannabis completely; 74.2% continued their pattern of regular use. Thus, the higher the baseline use pattern, the higher was the probability of continued or heavier use during follow-up. (3) Although the cumulative life-time incidence for DSM-IV cannabis abuse (3.5%) in this age group was low, it is noteworthy that complete diagnostic remissions were relatively rare (31.7% for dependence, 41.1% for abuse). (4) There was considerable concurrent use of other drugs. CONCLUSIONS: Cannabis use was almost as widespread in this sample of adolescents in Germany as in similar age groups in metropolitan areas of North America. There was a relatively low spontaneous remission rate among regular and repeated users. Cannabis use in adolescence appears to be less transient than many people would believe.
Adolescent↗
Covariates of cannabis use progression in a representative population sample of adolescents: a prospective examination of vulnerability and risk factors.
UNLABELLED: AIMS/DESIGN: This study reports findings concerning risk factors for first, "repeated" and "regular" use of cannabis in respondents (N = 1228) who were aged 14-17 years at the outset (i.e. at "baseline") as part of a longitudinal prospective community study (EDSP). Risk factors were assessed at baseline or by separate interviews with the respondents' parents. Cumulative life-time cannabis use was the main outcome measure in this study--assessed by information from both the baseline and the follow-up investigation at an average of 19.7 months later. A cumulative logistic regression model was used to estimate associations. FINDINGS: Using seven of a total of 25 variables examined, the final model classified 72.1% of respondents correctly. Family history of substance use disorders, self-esteem and competence, unconditional commitment to not using drugs, immediate availability of drugs, peer group drug use and previous history of nicotine dependence and alcohol use disorders all contributed significantly to the final model, predicting the progression to cannabis use from "no use", to "one time only", "repeated use", and "regular use". CONCLUSION: In addition to well-documented risk factors such as peer group pressure, availability, low self-esteem and competence, findings suggest that family history and prior experiences with legal drugs play a significant role in the early development of cannabis consumption in teenagers.
Adolescent↗
Acute normovolaemic haemodilution vs controlled hypotension for reducing the use of allogeneic blood in patients undergoing radical prostatectomy.
Blood loss in patients undergoing radical prostatectomy may be substantial. In a randomized, prospective study, we assessed two methods of reducing the need for allogeneic blood transfusion with regard to efficacy and costs. Sixty patients undergoing retropubic radical prostatectomy were allocated randomly to one of three groups. In group 1 (n = 20), acute normovolaemic haemodilution (ANH) was initiated after induction of anaesthesia; autologous blood 15 ml kg-1 was withdrawn and replaced by colloid solutions (gelatin) to maintain haemodynamic stability. In group 2 (n = 20), controlled hypotension was established using sodium nitroprusside (target mean arterial pressure (MAP) approximately 50 mm Hg). Group 3 (n = 20), without manipulations, served as a control group. Troponin T (TnT), a sensitive marker for myocardial ischaemia, and various coagulation variables were measured in the perioperative period. Packed red blood cells (PRBC) were given when haemoglobin concentration was less than 7 g dl-1. Cost calculations did not include hospital overhead costs or staff costs. In the ANH group, mean 1278 (SD 150) ml of autologous blood were withdrawn. Significantly more volume was infused in the ANH patients (gelatin 2450 (550) ml) than in the two other groups. Coagulation data (platelet count, activated partial thromboplastin time (aPTT), fibrinogen, antithrombin III (AT III), D-dimers) did not differ significantly between the three groups. The hypotension group had significantly lower blood loss (1260 (570) ml), whereas the ANH (1820 (680) ml) and control group (1920 (590) ml) did not differ significantly. Patients in the hypotension group needed significantly less PRBC (total 14 units; 75% of patients did not need PRBC) than the ANH (total 21 units; 55% of patients did not need PRBC) or control patients (total 28 units; 40% of patients did not need PRBC). Total costs were lowest in the hypotension group (41% less than in the control patients) (P < 0.05). We conclude that the use of hypotension during radical prostatectomy resulted in approximately 40% reduction in total transfusion costs. ANH was less effective and more costly than controlled hypotension.
Aged↗
The effects of sodium nitroprusside-induced hypotension on splanchnic perfusion and hepatocellular integrity.
UNLABELLED: The purpose of our study was to investigate the effects of sodium nitroprusside-induced hypotension on splanchnic perfusion and hepatocellular integrity. Thirty patients undergoing radical prostatectomy were allocated randomly to a sodium nitroprusside (SNP) or control group (control). Regional pco2 was measured using gastric tonometry, and the regional to arterial difference in partial pressure of CO2 and intramucosal pH were calculated. The cytosolic liver enzyme alpha-glutathione S-transferase and standard liver enzyme markers (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase) were also measured. Mean arterial pressure in the SNP group was 50 mm Hg for 97 min during surgery. A significant increase from baseline in regional pco2 (from 40.0+/-4.2 mm Hg to 45.3+/-1.3 mm Hg) and regional to arterial difference in partial pressure of CO2 (from 4.1+/-1.1 mm Hg to 9.7+/-1.4 mm Hg) was seen at 90 min after skin incision only in the SNP group. Intramucosal pH decreased significantly from 7.40+/-0.02 to 7.35+/-0.03 during the same period in this group. Tonometric variables returned to baseline values within 2 h postoperatively. Alpha-glutathione S-transferase concentrations increased significantly in the SNP group from baseline to peak concentrations at the end of surgery (SNP: 9.93+/-4.94 microg/L; control: 5.85+/-1.86 microg/L). A return to baseline values was seen 24 h postoperatively. No significant changes in standard liver enzyme markers were seen throughout the study period. It is concluded, that splanchnic perfusion was transiently impaired during controlled hypotension. This is supported by significant changes in tonometric data. Increased serum levels of alpha-glutathione S-transferase may indicate a disturbance in hepatocellular integrity. IMPLICATIONS: We studied gastric mucosal tonometry and the cytosolic liver enzyme alpha-glutathione S-transferase to evaluate the effects of controlled hypotension induced by sodium nitroprusside on splanchnic perfusion and hepatocellular integrity. Splanchnic perfusion decreased and alpha-glutathione S-transferase increased during and after a hypotensive period, but returned to baseline values within the first postoperative day, indicating a transient impairment of splanchnic perfusion and hepatocellular integrity.
Antihypertensive Agents↗
Evaluation of critical thinking in a baccalaureate nursing program.
The assessment of critical thinking traditionally has been accomplished through observation of students by faculty in clinical settings and evaluation of written patient assessments and care plans. Quantitative measurement has become a current focus of nurse educators. The purpose of this cross-sectional study was to compare and contrast critical thinking abilities in beginning and graduating nursing students using the California Critical Thinking Skills Test (CCTST) and the California Critical Thinking Disposition Inventory (CCTDI). The CCTST revealed a significant difference in critical thinking from the sophomore year to the senior year. There also were significant differences between sophomores and seniors on the overall score for the CCTDI, with subtest differences in truth-seeking, analyticity, self-confidence, and inquisitiveness.
Adult↗
Comorbidity in primary care: presentation and consequences.
Comorbidity is a well-established phenomenon in depressive disorders, and it is widely agreed that the majority of depressive disorders examined in both primary care and the general population are not "pure." This article reviews comorbidity findings in general population and primary care surveys. The implications of comorbid depressive disorders are discussed in terms of their presentation and recognition in primary care, patterns of course and outcome, and associated impairments and disabilities. Data from a World Health Organization study, conducted in primary health clinics in 15 countries, demonstrate that 62% of all depressive cases also suffer from at least one other current mental disorder and that the primary reason for patient visits is rarely of a psychological nature, with the majority of attendees complaining primarily of somatic symptoms (41%), pains (37%), and fatigue and sleep problems (12%). Similar results are presented from 2 recent large representative population surveys, the National Comorbidity Survey and the Early Developmental Stages of Psychopathology Study. The implications of such comorbidity are viewed from various perspectives: the form of depressive presentations in primary care, the recognition of depression in health care, and health services utilization, impairments and disabilities, and course and outcome.
Adolescent↗
Shaping space: the possible and the attainable in RNA genotype-phenotype mapping.
Understanding which phenotypes are accessible from which genotypes is fundamental for understanding the evolutionary process. This notion of accessibility can be used to define a relation of nearness among phenotypes, independently of their similarity. Because of neutrality, phenotypes denote equivalence classes of genotypes. The definition of neighborhood relations among phenotypes relies, therefore, on the statistics of neighborhood relations among equivalence classes of genotypes in genotype space. The folding of RNA sequence (genotypes) into secondary structures (phenotypes) is an ideal case to implement these concepts. We study the extent to which the folding of RNA sequence induces a "statistical topology" on the set of minimum free energy secondary structures. The resulting nearness relation suggests a notion of "continuous" structure transformation. We can, then rationalize major transitions in evolutionary trajectories at the level of RNA structures by identifying those transformations which are irreducibly discontinuous. This is shown by means of computer simulations. The statistical topology organizing the set of RNA shapes explains why neutral drift in sequence space plays a key role in evolutionary optimization.
Animals↗
Continuity in evolution: on the nature of transitions.
To distinguish continuous from discontinuous evolutionary change, a relation of nearness between phenotypes is needed. Such a relation is based on the probability of one phenotype being accessible from another through changes in the genotype. This nearness relation is exemplified by calculating the shape neighborhood of a transfer RNA secondary structure and provides a characterization of discontinuous shape transformations in RNA. The simulation of replicating and mutating RNA populations under selection shows that sudden adaptive progress coincides mostly, but not always, with discontinuous shape transformations. The nature of these transformations illuminates the key role of neutral genetic drift in their realization.
Base Sequence↗
Structure, content and reliability of the Munich-Composite International Diagnostic Interview (M-CIDI) substance use sections.
After reviewing currently available diagnostic assessment instruments for substance use disorders this paper describes the format and structure of the Munich-Composite International Diagnostic Interview (M-CIDI) substance disorder section. In addition, the test-retest reliability of diagnoses and criteria for nicotine, alcohol, illegal and prescription drugs, is reported. Findings obtained in community sample of adolescents and young adults indicate that the substance section is acceptable for almost all types of respondents, efficient in terms of time and ease of administration as well as reliable in terms of consistency of findings over time. The test-retest reliability over a period of an average of 1 month, as examined by two independent interviewers indicates good-to-excellent kappa values for all substance disorders assessed, with significant kappa values ranging between 0.55 for drug abuse and 0.83 for alcohol abuse. There was also fairly consistently high agreement for the assessment of single DSM-IV diagnostic criteria for abuse and dependence as well as the M-CIDI quantity-frequency and time-related questions. To conclude, although - unlike previous studies - this study was conducted in a community sample and not in patients and used considerably longer time intervals of more than a month between investigations, our M-CIDI reliability findings are at least as high as those from previous studies.
Adolescent↗
Is the use of ecstasy and hallucinogens increasing? Results from a community study.
UNLABELLED: This report presents findings of a community survey of 3,021 adolescents and young adults aged 14-24 years in Munich, Germany, carried out to determine the prevalence of use and abuse of and dependence on ecstasy, amphetamines and hallucinogens. The response rate was 71%. RESULTS: (1) In 1995, 4% of the male and 2.3% of the female respondents aged 14-24 reported the use of ecstasy. Ecstasy-related substances (amphetamines and chemically related substances) were reported by 3.6% of men and 1.6% of women. Hallucinogens were reported slightly less frequently by 3% of men and about 2% of women (LSD combined with others). (2) Compared to findings from a 1990 survey this constitutes a substantial, at least twofold, increase in consumption rate of both types of substances. (3) Among lifetime users of both ecstasy and related substances as well as hallucinogens about two thirds could be regarded as regular users. (4) The prevalence of DSM-IV abuse and dependence on ecstasy and related substances is about 1%, identical to rates of hallucinogen abuse and dependence. Findings also point to a significant dependence potential for both substances. (5) Furthermore, considerable overlap between the two substances was found. CONCLUSION: Our study suggests a substantial increase in both the use of ecstasy and related substances as well as hallucinogens. The data further suggest that the increase is strongest in younger age groups, but the risk of first use of these substances continues to be present up to the age of 24 years. The higher proportion of women contributing to this increase is noteworthy.
Adolescent↗