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PubMed2006

Pharmacokinetics of intravenous immunoglobulin: a systematic review.

BACKGROUND: Intravenous immunoglobulin (IGIV) is used in the treatment of a wide variety of immune disorders. To our knowledge, no comprehensive or systematic review on the pharmacokinetics of IGIV has been published despite the availability of many published individual studies. OBJECTIVE: To systematically review published studies of the pharmacokinetics of IGIV. METHODOLOGY: We conducted a search of PubMed/MEDLINE from January 1966-September 2005 and EMBASE from January 1980-September 2005 for English-language articles on the pharmacokinetics of IGIV. This search was supplemented by a bibliographic review of all relevant articles. RESULTS: Data elements extracted from these articles included study design, number of study subjects, indication for IGIV therapy, IGIV treatment regimen (formulation, dosage, and duration), pharmacokinetic parameters (clearance, volume of distribution, elimination rate constant, and half-life), analytic methodology, pharmacokinetic model, and blood sampling times. The United States Preventive Services Task Force rating scale was used to categorize the 50 pertinent citations identified in our literature search. According to the rating scale, 12 studies were level I (prospective, randomized, controlled studies), 3 were level II-1 (prospective, nonrandomized, controlled studies), 30 were level II-2 (prospective, nonrandomized, uncontrolled [cohort] studies), and 5 were level III (case reports or descriptive studies). CONCLUSION: The pharmacokinetics of IGIV shows considerable intra- and interpopulation variability among patients with normal immunoglobulin levels, patients with primary immunodeficiency diseases, bone marrow transplant recipients, patients with immune deficiency due to chronic lymphocytic leukemia or multiple myeloma, very low birth weight neonates, neonates with suspected sepsis, high-risk infants in the neonatal intensive care unit, high-risk infants with cardiopulmonary disease, children with cryptogenic West or Lennox-Gastaut syndrome, women and infants with fetal alloimmune thrombocytopenia, and women with recurrent spontaneous abortions. Despite the large number of studies characterizing the pharmacokinetics of IGIV, major literature gaps include lack of information on IGIV clearance or area under the curve parameters and target serum immunoglobulin G concentrations. Further study is needed to rigorously characterize the pharmacokinetic properties of IGIV in a range of patient populations.

Clinical Trials as Topic↗

PubMed2004

Parent report of reading to young children.

OBJECTIVE: The purpose of this study was to investigate the predictors and frequency of book-sharing activities in a nationally representative sample of families with young children and to examine the extent to which parents report that pediatric health care providers are addressing early literacy activities. METHODS: This study analyzed data from the 2000 National Survey of Early Childhood Health (NSECH), a telephone survey of 2068 parents of children aged 4 to 35 months. Parents were queried about the frequency of reading with their child, whether their pediatric provider discussed reading in the past year, and, if not, whether a discussion of the importance of reading to their child would have been helpful. Descriptive statistics, bivariate analyses, and multivariate logistic regression to identify predictors of daily reading among parents of young children nationally were used. RESULTS: Approximately 52% of young children are reportedly read to every day by a parent. Significant predictors of daily reading include older child's age (19-35 months; odds ratio [OR]: 1.77; 95% confidence interval [CI]: 1.18-2.65, as compared with 4-9 months), maternal education greater than high school (OR: 2.00; 95% CI: 1.24-3.22), greater number of children's books in the home (OR: 1.01; 95% CI: 1.00-1.01), and discussion of reading by the pediatric provider (OR: 1.66; 95% CI: 1.23-2.24). Lower odds of daily reading are found for maternal full-time working status (OR: 0.68; 95% CI: 0.49-0.95), black race/ethnicity (OR: 0.61; 95% CI: 0.41-0.91), Hispanic race/ethnicity (OR: 0.56; 95% CI: 0.37-0.86), Spanish language-dominant parents (OR: 0.37; 95% CI: 0.22-0.62), and >1 child in the household (2 children OR: 0.68, 95% CI: 0.48-0.97; 3 children OR: 0.53, 95% CI: 0.35-0.82). Approximately 37% of parents of young children stated that their child's pediatric provider had not discussed reading with them. Nearly half (47%) of these parents indicated that they would have found such a discussion helpful. CONCLUSIONS: Family context and daily reading routines are important for a child's early literacy development. This national study identifies how family characteristics and routines are associated with the family's literacy orientation. The analysis also indicates that a large percentage of parents with young children who do not read daily believe that it would be helpful to discuss the importance of reading with their child's pediatric provider.

Age Factors↗

PubMed2002

Human brain plasticity: evidence from sensory deprivation and altered language experience.

The results from the language studies taken as a whole point to different developmental time courses and developmental vulnerabilities of aspects of grammatical and semantic/lexical processing. They thus provide support for conceptions of language that distinguish these subprocesses within language. Similarly, following auditory deprivation, processes associated with the dorsal visual pathway were more altered than were functions associated with the ventral pathway, providing support for conceptions of visual system organization that distinguish functions along these lines. Could the effects observed in blind and deaf adults be accounted for, at least in part, by the redundant connectivity of the immature human brain? One way we tested this hypothesis was to study the differentiation of visual and auditory sensory responses in normal development (Neville, 1995). In normal adults, auditory stimuli elicit ERP responses that are large over temporal brain regions but small or absent over occipital regions. By contrast, in 6-month-old children we observed that auditory ERPs are equally large over temporal and visual brain regions, consistent with the idea that there is less specificity and more redundancy of connections between the auditory and visual cortex at this time. Between 6 and 36 months, however, we observed a gradual decrease in the amplitude of the auditory ERP over visual areas, while the amplitude over the temporal areas was unchanged. These results suggest that early in human development, there exists a redundancy of connections between auditory and visual areas and that this overlap gradually decreases after birth. This loss of redundancy may be a boundary condition that determines when sensory deprivation can result in alterations in the organization of remaining sensory systems. The considerable variability in timing of sensitive periods may also be in part due to temporal differences in the occurrence of redundancy within different systems. Ongoing studies of infants and children employing different types of stimuli will test for the specificity of these effects (Mitchell et al., 1999). Differences in the degree of plasticity may also be due to differences in the overall level of redundant connectivity within different systems. For example, it may be that aspects of sensory systems that are specialized for high spatial acuity (e.g., central vision and central audition) exhibit fewer developmental redundancies, decreased modifiability and more specificity than those displaying less acuity and precision (e.g., peripheral representations within vision and audition). There is some evidence for this hypothesis within the visual system (Chalupa and Dreher, 1991). In addition, there may be molecular differences between systems displaying different levels and patterns of experience-dependent plasticity. It is of interest that all levels of the dorsal pathway of the visual system, which in the studies reviewed here shows a high level of modifiability, displays strong immunoreactivity for the monoclonal antibody CAT 301 in macaque monkeys (DeYoe et al., 1990). By contrast there is very little labeling within the ventral visual pathway. Moreover, the expression of CAT 301 immunoreactivity shows marked experience-dependent plasticity, suggesting it may play a role in the guidance and/or stabilization of synaptic structure (Sur et al., 1988). Further research along these lines within the auditory system and in animal models of sensory deprivation and other developmental disorders may elucidate the role of specific molecular factors in the developmental plasticity of different neural systems. A related, more general hypothesis that may account for the different patterns of plasticity within both vision and language is that systems employing fundamentally different learning mechanisms (perhaps mediated by different anatomical and molecular substrates) display different patterns of developmental plasticity. It may be that systems that display experience-dependent change throughout life, including the topography of sensory maps (Merzenich et al., 1988; Gilbert, 1995; Kaas, 1995), lexical acquisition (i.e. object-word associations), and the establishment of form, face, and object representations (i.e., ventral pathway functions) rely upon very general, associative learning mechanisms that permit learning and adaptation throughout life. By contrast, systems that are important for computing dynamically shifting relations among locations, objects and events (including the dorsal visual pathway and the systems of the brain that mediate grammar) appear dependent on and modifiable by experience primarily during more limited periods in development. This could account for both the greater developmental deficits and enhancements of dorsal pathway function following various developmental anomalies and for the greater effects of altered language experience on grammatical functions. Further research is necessary to characterize systems that become constrained in this way and those that can be modified throughout life. This type of developmental evidence can contribute to fundamental descriptions of the architecture of different cognitive systems and can guide future studies of the cellular and molecular mechanisms important in neuroplasticity. Additionally, in the long run, they may contribute to the design of educational and habilitative programs for both normally and abnormally developing children.

Adaptation, Physiological↗

PubMed2005

A Java application for tissue section image analysis.

The medical industry has taken advantage of Java and Java technologies over the past few years, in large part due to the language's platform-independence and object-oriented structure. As such, Java provides powerful and effective tools for developing tissue section analysis software. The background and execution of this development are discussed in this publication. Object-oriented structure allows for the creation of "Slide", "Unit", and "Cell" objects to simulate the corresponding real-world objects. Different functions may then be created to perform various tasks on these objects, thus facilitating the development of the software package as a whole. At the current time, substantial parts of the initially planned functionality have been implemented. Getafics 1.0 is fully operational and currently supports a variety of research projects; however, there are certain features of the software that currently introduce unnecessary complexity and inefficiency. In the future, we hope to include features that obviate these problems.

Cytological Techniques↗

PubMed2005

Does neostigmine administration produce a clinically important increase in postoperative nausea and vomiting?

Neostigmine is used to antagonize neuromuscular blocker-induced residual neuromuscular paralysis. Despite the findings of a previous meta-analysis, the effect of neostigmine on postoperative nausea and vomiting remains unresolved. We reevaluated the effect of neostigmine on postoperative nausea and vomiting while considering the different anticholinergics as potentially confounding factors. We performed a systematic literature search using MEDLINE, Embase, Cochrane library, reference listings, and hand searching with no language restriction through December 2004 and identified 10 clinical, randomized, controlled trials evaluating neostigmine's effect on postoperative nausea and vomiting. Data on nausea or vomiting from 933 patients were extracted for the early (0-6 h), delayed (6-24 h), and overall (0-24 h) postoperative periods and analyzed with RevMan 4.2 (Cochrane Collaboration, Oxford, UK) and multiple logistic regression analysis. The combination of neostigmine with either atropine or glycopyrrolate did not significantly increase the incidence of overall (0-24 h) vomiting (relative risk, 0.91; 95% confidence interval, 0.70-1.18; P = 0.48) or nausea (relative risk, 1.24; 95% confidence interval, 0.98-1.59; P = 0.08). Multiple logistic regression analysis indicated that there was not a significant increase in the risk of vomiting with large compared with small doses of neostigmine. Contrasting a previous analysis, we conclude that there is insufficient evidence to conclude that neostigmine increases the risk of postoperative nausea and vomiting.

Humans↗

PubMed2001

Conceptual search in electronic patient record.

Search by content in a large corpus of free texts in the medical domain is, today, only partially solved. The so-called GREP approach (Get Regular Expression and Print), based on highly efficient string matching techniques, is subject to inherent limitations, especially its inability to recognize domain specific knowledge. Such methods oblige the user to formulate his or her query in a logical Boolean style; if this constraint is not fulfilled, the results are poor. The authors present an enhancement to string matching search by the addition of a light conceptual model behind the word lexicon. The new system accepts any sentence as a query and radically improves the quality of results. Efficiency regarding execution time is obtained at the expense of implementing advanced indexing algorithms in a pre-processing phase. The method is described and commented and a brief account of the results illustrates this paper.

Artificial Intelligence↗

PubMed1995

A speed limit for evolution.

An upper bound on the speed of evolution is derived. The bound concerns the amount of genetic information which is expressed in observable ways in various aspects of the phenotype. The genetic information expressed in some part of the phenotype of a species cannot increase faster than a given rate, determined by the selection pressure on that part. This rate is typically a small fraction of a bit per generation. Total expressed genetic information cannot increase faster than a species-specific rate--typically a few bits per generation. These bounds apply to all aspects of the phenotype, but are particularly relevant to cognition. As brains are highly complex, we expect large amounts of expressed genetic information in the brain--of the order of 100 kilobytes--yet evolutionary changes in brain genetic information are only a fraction of a bit per generation. This has important consequences for cognitive evolution. The limit implies that the human brain differs from the chimpanzee brain by at most 5 kilobytes of genetic design information. This is not enough to define a Language Acquisition Device, unless it depends heavily on pre-existing primate symbolic cognition. Subject to the evolutionary speed limit, in changing environments a simple, modular brain architecture is fitter than more complex ones. This encourages us to look for simplicity in brain design, rather than expecting the brain to be a patchwork of ad hoc adaptations. The limit implies that pure species selection is not an important mechanism of evolutionary change.

Animals↗

PubMed2001

Tricross : using dot-plots in sequence-id space to detect uncataloged intergenic features.

MOTIVATION: The process of determining the functional sequence content of an organism is confounded by several factors. Large protein coding sequences are relatively easy to find by statistical methods. Smaller proteins however may escape detection due to their size falling below some arbitrary researcher-defined minimum cutoff, or the inability to precisely define a promoter, or translational start (Delcher et al., Nucleic Acids Res., 27, 4636-4641, 1999). Promoter and regulatory sequences themselves are difficult to define due to a significant amount of allowable sequence variation, as well as a probable lack of any completely accurate whole-organismal gene catalogs to date. Finally, certain genes coding functional RNAs may have insufficient structural or sequence constraints to be detectable by normal sequence structure/pattern searching methods (Eddy and Rivas, Bioinformatics, 16, 583-605, 2000). In those cases where there are multiple closely related organisms that have been sequenced, there is additional information that may be used in the investigation of sequence content-that being the possible conserved nature of functional sequences between the organisms. We present a method for the utilization of this conserved information to detect genes and other potentially functional sequences that may be missed by standard ORF-calling, RNA finding, and pattern matching software. The tricross programs produce a multi-way cross comparison of three sets of sequences, determine which are conserved in all three sets, and produce a graphical (Virtual Reality Modelling Language-VRML; (ISO/IEC 14772-1: 1997, VDC), 1997) representation as well as alignments of all sequence triples found. The software can also be applied to a pair of sequence sets, though the noise in the results increases. RESULTS: Tricross has been used to examine the intergenic-sequence content of the three archaeal Pyrococcus genomes to determine the most highly related sequences remaining between the annotated protein and RNA coding sequences. Set to relatively stringent similarity requirements for the search, tricross found 101 intergenic sequences conserved among the three organisms. Interestingly, 29 of these appear to contain members of a family of small RNA molecules (Kiss-Laszlo et al., EMBO J., 17, 797-807, 1998) only recently discovered in the Archaea (Armbruster, OSU, Diss., 1988; Omer et al., Science, 288, 517-522, 2000; Gaspin et al., J. Mol. Biol., 297, 895-906, 2000). While some of the remaining 72 appear to be individual highly conserved promoter sequences, others have no currently known biological significance. Although originally developed to facilitate the examination of intergenic sequences, none of the tricross logic is inherently specific to intergenic sequences. The software can also be applied to gene sequences, and has been used to produce inter-genomic gene order dot-plots for Haemophilus influenzae (Fleischmann et al., Science, 269, 496-512, 1995) versus H.ducreyi (unpublished data), and Neisseria meningiditis Z2491 (serogroup A) (Parkhill et al., Nature, 404, 502-506, 2000) versus Neisseria meningiditis Z58 (serogroup B) (Tettelin et al., Science, 287, 1809-1815, 2000) versus Neisseria gonorrhoeae (Lewis et al., http://micro-gen.ouhsc.edu/, 2000). AVAILABILITY: The tricross software package is available from http://www.biosci.ohio-state.edu/~ray/bioinformatics/tricross.html. CONTACT: ray@biosci.ohio-state.edu; daniels.7@osu.edu; munsonr@pediatrics.ohio-state.edu SUPPLEMENTARY INFORMATION: Additional data from the cross-genomic comparisons examined in the discussion section are linked from http://www.biosci.ohio-state.edu/~ray/bioinformatics/tricross.html.

Base Sequence↗

PubMed2004

Combination estrogen-progestin contraceptives and body weight: systematic review of randomized controlled trials.

OBJECTIVE: Many women and clinicians believe that combination estrogen-progestin contraceptive use can lead to weight gain. This concern can deter women from starting hormonal contraception or lead to premature quitting. This review evaluated the association between combination contraceptive use and change in body weight. DATA SOURCES: The computerized databases CENTRAL, MEDLINE, EMBASE, Popline, and LILACS (from their inception to 2002) were used to conduct this review. Known investigators and manufacturers were contacted for information about other trials not discovered in the database search. METHODS OF STUDY SELECTION: All English-language, randomized controlled trials measuring weight change that were at least 3 treatment cycles in duration and that compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length were eligible for inclusion. Of the 570 reports of randomized controlled trials of eligible interventions that were identified, 42 trials were included in the systematic review. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently abstracted data from the eligible trials using a standard form. Depending on the data available, the weighted mean difference using a fixed effect model with 95% confidence intervals was calculated for the mean change in weight between baseline and posttreatment measurements or the Peto odds ratio with 95% confidence intervals was calculated by using the proportion of women who gained or lost more than a specified amount of weight. The 3 placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons from the 40 trials that compared 2 or more combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups when this factor was studied. CONCLUSION: Available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.

Adult↗

PubMedDate not supplied

[Model to predict staffing for anesthesiology and post-anesthesia intensive care units and pain clinics].

Human resources account for a large part of the budgets of anesthesia and post-anesthesia intensive care units and pain clinics (A-PICU-PC). Adequate staffing is a key factor in providing for both effective care and professional staff development. Changes in professional responsibilities have rendered obsolete the concept of one anesthesiologist per operating room. Duties must be analyzed objectively to facilitate understanding between hospital administrators and A-PICU-PC chiefs of service when assigning human resources. The Catalan Society of Anesthesiology, Post-anesthesia Intensive Care and Pain Therapy has developed a model for estimating requirements for A-PICU-PC staffing based on three factors: 1) Definition of staff positions that must be filled and criteria for assigning human resources; 2) Estimation of non-care-related time required by the department for training, teaching, research and internal management, and 3) Estimation of staff required to cover absences from work for vacations, personal leave or illness. The model revealed that the ratio of number of staff positions to number of persons employed by an A-PICU-PC is approximately 1.3. Differences in the nature of services managed by an A-PICU-PC or the type of hospital might change the ratio slightly. The model can be applied universally, independently of differences that might exist among departments. Widespread application would allow adoption of a common language to be used by health care managers and A-PICU-PC departments when discussing a basis for consensus about our specialty.

Anesthesiology↗

PubMed2005

Whorf hypothesis is supported in the right visual field but not the left.

The question of whether language affects perception has been debated largely on the basis of cross-language data, without considering the functional organization of the brain. The nature of this neural organization predicts that, if language affects perception, it should do so more in the right visual field than in the left visual field, an idea unexamined in the debate. Here, we find support for this proposal in lateralized color discrimination tasks. Reaction times to targets in the right visual field were faster when the target and distractor colors had different names; in contrast, reaction times to targets in the left visual field were not affected by the names of the target and distractor colors. Moreover, this pattern was disrupted when participants performed a secondary task that engaged verbal working memory but not a task making comparable demands on spatial working memory. It appears that people view the right (but not the left) half of their visual world through the lens of their native language, providing an unexpected resolution to the language-and-thought debate.

Adult↗

PubMed2004

Knowledge discovery by automated identification and ranking of implicit relationships.

MOTIVATION: New relationships are often implicit from existing information, but the amount and growth of published literature limits the scope of analysis an individual can accomplish. Our goal was to develop and test a computational method to identify relationships within scientific reports, such that large sets of relationships between unrelated items could be sought out and statistically ranked for their potential relevance as a set. RESULTS: We first construct a network of tentative relationships between 'objects' of biomedical research interest (e.g. genes, diseases, phenotypes, chemicals) by identifying their co-occurrences within all electronically available MEDLINE records. Relationships shared by two unrelated objects are then ranked against a random network model to estimate the statistical significance of any given grouping. When compared against known relationships, we find that this ranking correlates with both the probability and frequency of object co-occurrence, demonstrating the method is well suited to discover novel relationships based upon existing shared relationships. To test this, we identified compounds whose shared relationships predicted they might affect the development and/or progression of cardiac hypertrophy. When laboratory tests were performed in a rodent model, chlorpromazine was found to reduce the progression of cardiac hypertrophy.

Abstracting and Indexing↗

PubMed2006

Somali and Oromo refugee women: trauma and associated factors.

AIM: This paper reports a study identifying the demographic characteristics, self-reported trauma and torture prevalence, and association of trauma experience and health and social problems among Somali and Oromo women refugees. BACKGROUND: Nearly all refugees have experienced losses, and many have suffered multiple traumatic experiences, including torture. Their vulnerability to isolation is exacerbated by poverty, grief, and lack of education, literacy, and skills in the language of the receiving country. METHOD: Using data from a cross-sectional population-based survey, conducted from July 1999 to September 2001, with 1134 Somali and Oromo refugees living in the United States of America, a sub-sample of female participants with clearly identified parenting status (n = 458) were analysed. Measures included demographics, history of trauma and torture, scales for physical, psychological, and social problems, and a post-traumatic stress symptom checklist. FINDINGS: Results indicated high overall trauma and torture exposure, and associated physical, social and psychological problems. Women with large families reported statistically significantly higher counts of reported trauma (mean 30, P < 0.001) and torture (mean 3, P < 0.001), and more associated problems (P < 0.001) than the other two groups. Women who reported higher levels of trauma and torture were also older (P < 0.001), had more family responsibilities, had less formal education (P < 0.001) and were less likely to speak English (P < 0.001). CONCLUSION: These findings suggest a need for nurses, and especially public health nurses who work with refugee and immigrant populations in the community, to develop a more comprehensive understanding of the range of refugee women's experiences and the continuum of needs post-migration, particularly among older women with large family responsibilities. Nurses, with their holistic framework, are ideally suited to partner with refugee women to expand their health agenda beyond the biomedical model to promote healing and reconnection with families and communities.

Adaptation, Psychological↗

PubMed2006

The temporal signatures of semantic and phonological activations for Chinese sublexical processing: an event-related potential study.

A large number of Chinese characters are made up by pairing a semantic radical and a phonetic radical. The phonetic radical usually gives a phonological clue for the pronunciation of the whole character but does not contribute to its meaning. Using an event-related potential (ERP) measurement, the present study was able to trace the very intricate interplay between phonological and semantic information embedded in the phonetic radical. It was found that, within the first 50 to 100 ms of perceiving the character, the semantic information of the phonetic radical was better preserved when the constituent phonetic radical provided a valid phonological clue (e.g., regular phonogram) than when it contained an invalid phonetic cue (e.g., irregular phonogram). However, no trace of semantic information from the phonetic radical was preserved after 300 ms. These ERP results detail the neuropsychological steps in reading Chinese and support the framework of the lexical constituent model.

Adult↗

PubMed2002

Maximum speed of pitch change and how it may relate to speech.

How fast speakers can change pitch voluntarily is potentially an important articulatory constraint for speech production. Previous attempts at assessing the maximum speed of pitch change have helped improve understanding of certain aspects of pitch production in speech. However, since only "response time"--time needed to complete the middle 75% of a pitch shift--was measured in previous studies, direct comparisons with speech data have been difficult. In the present study, a new experimental paradigm was adopted in which subjects produced rapid successions of pitch shifts by imitating synthesized model pitch undulation patterns. This permitted the measurement of the duration of entire pitch shifts. Native speakers of English and Mandarin participated as subjects. The speed of pitch change was measured both in terms of response time and excursion time-time needed to complete the entire pitch shift. Results show that excursion time is nearly twice as long as response time. This suggests that physiological limitation on the speed of pitch movement is greater than has been recognized. Also, it is found that the maximum speed of pitch change varies quite linearly with excursion size, and that it is different for pitch rises and falls. Comparisons of present data with data on speed of pitch change from studies of real speech found them to be largely comparable. This suggests that the maximum speed of pitch change is often approached in speech, and that the role of physiological constraints in determining the shape and alignment of F0 contours in speech is probably greater than has been appreciated.

Adolescent↗

PubMed2000

Search for a new description of protein topology and local structure.

A novel description of protein structure in terms of the generalized secondary structure elements (GSSE) is proposed. GSSE's are defined as fragments of the protein structure where the chain doesn't radically change its direction. In this new language, global protein topology becomes a particular arrangement of the relatively small number of large, rod like GSSE's. Protein topology can be described by an adjacency matrix giving information, which GSSE's are close in space to each other and defining a graph, where GSSE's are equivalent to vertices and interactions between them to edges. The information about the local structure is translated into the local density of pseudo-Calpha atoms along the chain and the curvature of the chain. This new description has a number of interesting and useful features. For instance, enumeration theorems of graph theory can be used to estimate a number of possible topologies for a protein built from a given number of elements. Different topologies, including novel ones, can be generated from the known by various permutations of elements. Many new regularities in protein structures become suddenly visible in a new description. A new local structure description is more amenable to predictions and easier to use in fold predictions.

Animals↗

PubMed2000

Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: The Kame Project.

BACKGROUND: The relation between estrogen and cognition among postmenopausal women remains controversial. Also uncertain is whether the proposed association varies between women taking unopposed estrogen and those taking estrogen combined with progestin. OBJECTIVE: To determine whether unopposed estrogen and combined estrogen-progestin use were associated with the rate of cognitive change in a cohort of older, Japanese American, postmenopausal women. METHODS: A prospective observational study in a population-based cohort of older Japanese Americans (aged > or =65 years) living in King County, Washington. Cognitive performance was measured in 837 women at baseline (1992-1994) and 2-year follow-up (1994-1997) examinations using the 100-point Cognitive Abilities Screening Instrument (CASI). Least squares means general linear models were used to estimate the 2-year rate of cognitive change according to categories of postmenopausal estrogen use. RESULTS: Approximately half of this cohort (n=455) had never used estrogen at any time since menopause, 186 were past users, 132 were current unopposed estrogen users, and 64 were current estrogen-progestin users. The majority of current estrogen users were taking conjugated estrogens, and all women receiving combined therapy were taking medroxyprogesterone acetate. After adjusting for age, education, language spoken at the interview, surgical menopause, and baseline CASI score, women who had never used postmenopausal estrogen improved slightly on the CASI scale (mean adjusted change, 0.79; SEM, 0.19). This change was significantly greater for current unopposed estrogen users (mean adjusted change, 1.68; SEM, 0.36; P=.04) and significantly worse for current estrogen-progestin users (mean adjusted change, -0.41; SEM, 0.50; P =.02) compared with never users. The improvement observed in past users (mean adjusted change, 1.12; SEM, 0.29) was intermediate between the changes for never users and current unopposed estrogen users and not significantly greater than that for never users (P=.35). CONCLUSIONS: Our findings support a modest beneficial association between current unopposed estrogen use and the rate of cognitive change. We also observed a modest detrimental association between current estrogen-progestin use and the rate of cognitive change. The clinical significance of these modest differences, however, is uncertain. Data from large, long-term randomized trials are required before applying this information to the clinical setting.

Aged↗

PubMed2006

Enabling computer models of the heart for high-performance computers and the grid.

Although it is now feasible to compute multi-cellular models of the heart on a personal desktop or laptop computer, it is not feasible to undertake the detailed sweeps of high-dimensional parameter spaces required if we are to undertake in silico experimentation of the complex processes that constitute heart disease. For this research, modelling requirements move rapidly beyond the limit of commodity computers' resource both in terms of their memory footprint and the speed of calculation, so that multi-processor architectures must be considered. In addition, as such models have become more mature and have been validated against experimental data, there is increasing pressure for experimentalists to be able to make use of these models themselves as a key tool for hypothesis formulation and in planning future experimental studies to test those hypotheses. This paper discusses our initial experiences in a large-scale project (the Integrative Biology (IB) e-Science project) aimed at meeting these dual aims. We begin by putting the research in context by describing in outline the overall aims of the IB project, in particular focusing on the challenge of enabling novice users to make full use of high-performance resources without the need to gain detailed technical expertise in computing. We then discuss our experience of adapting one particular heart modelling package, Cellular Open Resource, and show how the solving engine of this code was dissected from the rest of the package, ported to C++ and parallelized using the Message-Passing Interface. We show that good parallel efficiency and realistic memory reduction can be achieved on simple geometries. We conclude by discussing lessons learnt in this process.

Action Potentials↗