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Use of monofilament in the detection of foot lesions in older adults.

The purpose of this study was to compare Semmes-Weinstein monofilament testing between elderly and young patients in both a diabetic and nondiabetic population. Monofilament mapping (10 g) was performed on 115 patients: 74 who were greater than 60 years of age (47 with diabetes) and 41 who were younger than 60 years (20 with diabetes). Sensations were assessed at 15 predefined pressure/risk points. Sensations were found to have perfect correlation between the same point on the left and right foot (r = 1.0) for each of the 15 points. The data for the 15 points were divided in 2 subsets: one for 8 points similar to a validated method and another with 7 new points on the dorsum and ankle area. Scores on both subsets differed significantly by age group (P < .0001) and diabetes status (P < .001), with older patients and patients with diabetes having higher scores. Analysis of covariance was used to estimate 15-point scores for the 4 combinations of age group and diabetes status, adjusting for foot ulceration, callus, deformity, and ischemia. In older patients without diabetes, each subset score was used to detect future neuropathy if 4 or more points were insensitive. The detections agreed in 37 of 47 cases. In all 10 cases of disagreement, the 7-point subset detected no neuropathy, suggesting that inclusion of the additional points could improve diagnostic specificity. The significant differences noted between young and old patients suggest the importance of aging-related changes, and raise questions about current scoring methods for detection of neuropathy in older adults with diabetes.

Adult↗

On parameter estimation of chaotic systems via symbolic time-series analysis.

Symbolic time-series analysis is used for estimating the parameters of chaotic systems. It is assumed that a "target model" (i.e., a discrete- or continuous-time description of the data-generating mechanism) is available, but with unknown parameters. A time series, i.e., a noisy, finite sequence of a measured (output) variable, is given. The proposed method first prescribes to symbolize the time series, i.e., to transform it into a sequence of symbols, from which the statistics of symbols are readily derived. Then, a symbolic model (in the form of a Markov chain) is derived from the data. It allows one to predict, in a probabilistic fashion, the time evolution of the symbol sequence. The unknown parameters are derived by matching either the statistics of symbols, or the symbolic prediction derived from data, with those generated by the (parametrized) target model. Three examples of application (the Henon map, a population model, and the Duffing system) prove that satisfactory results can be obtained even with short time series.

Algorithms↗

Incidence and outcomes of mental disorders in a regional population: the Northern Rivers Mental Health Study.

OBJECTIVES: To estimate the incidence of mental disorders in a cohort of previously symptom-free individuals who are representatives of a regional Australian population. To map changing patterns of diagnosis and comorbidity within the cohort over a 2 year period. METHOD: Two year follow-up of a community-based cohort drawn from a telephone screening of 9191 randomly selected adults. Subjects were administered a comprehensive face-to-face interview which included the Composite International Diagnostic Interview. A total of 1407 subjects were interviewed at baseline, and 968 subjects were reinterviewed (a 68.8% follow-up rate). RESULTS: There was considerable change in disorder status over the study period, and analysis of the Composite International Diagnostic Interview scoring suggests that these changes reflected real changes in symptomatology. Of subjects interviewed at both baseline and follow-up, 638 were classified as disorder-free at their entry to the study. After 2 years, 98 of these met criteria for a mental disorder during the preceding 12 months. After adjusting for sampling and gender, the 12 month incidence of any mental disorder among subjects who had been disorder-free 2 years previously was 9.95 per hundred person-years at risk. At baseline, a further 330 subjects met ICD-10 criteria for a mental disorder during the previous 12 months. Two years later, 167 of these subjects (50.6%) were disorder-free, and 163 still met the criteria for a mental disorder, although there had often been considerable change in their diagnosis. Subjects with a mental disorder at the commencement of the study were significantly more likely than those without a disorder to have a positive diagnosis 2 years later (p < 0.001). The number of diagnoses at baseline was a strong predictor of the number of diagnoses at follow-up (p < 0.001), and each additional comorbid diagnosis at baseline also increased the probability of a persisting disorder at follow-up (p < 0.001). CONCLUSIONS: Over a 2 year period, the majority of subjects with a mental disorder will become disorder-free, while a significant number of previously disorder-free individuals will develop a positive diagnosis. Health services need to be designed to meet this labile demand.

Absenteeism↗

Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.

Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsonism with multiple consanguinity loops in a genetically isolated population. Homozygosity mapping resulted in significant evidence for linkage on chromosome 1p36. Multipoint linkage analysis using MAPMAKER-HOMOZ generated a maximum LOD-score of 4.3, with nine markers spanning a disease haplotype of 16 cM. On the basis of several recombination events, the region defining the disease haplotype can be clearly separated, by > or =25 cM, from the more centromeric PARK6 locus on chromosome 1p35-36. Therefore, we conclude that we have identified on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early-onset parkinsonism.

Age of Onset↗

Diverse variation of reproductive barriers in three intraspecific rice crosses.

Reproductive barriers are thought to play an important role in the processes of speciation and differentiation. Asian rice cultivars, Oryza sativa, can be classified into two main types, Japonica and Indica, on the basis of several characteristics. The fertility of Japonica-Indica hybrids differs from one cross to another. Many genes involved in reproductive barriers (hybrid sterility, hybrid weakness, and gametophytic competition genes) have been reported in different Japonica-Indica crosses. To clarify the state of Japonica-Indica differentiation, all reproductive barriers causing deviation from Mendelian segregation ratios in F(2) populations were mapped and compared among three different Japonica-Indica crosses: Nipponbare/Kasalath (NK), Fl1084/Dao Ren Qiao (FD), and Fl1007/Kinandang puti (FK). Mapping of reproductive barriers was performed by regression analysis of allele frequencies of DNA markers covering the entire genome. Allele frequencies were explained by 33 reproductive barriers (15 gametophytic and 18 zygotic) in NK, 32 barriers (15 gametophytic and 17 zygotic) in FD, and 37 barriers (19 gametophytic and 18 zygotic) in FK. The number of reproductive barriers in the three crosses was similar; however, most of the barriers were mapped at different loci. Therefore, these reproductive barriers formed after Japonica-Indica differentiation. Considering the high genetic similarity within Japonica and Indica cultivars, the differences in the reproductive barriers of each cross were unexpectedly numerous. The reproductive barriers of Japonica-Indica hybrids likely evolved more rapidly than other genetic elements. One possible force responsible for such rapid evolution of the barriers may have been the domestication of rice.

Gene Frequency↗

Genomic Divergence Shaped the Genetic Regulation of Meiotic Homologous Recombination in Brassica Allopolyploids.

The tight regulation of meiotic recombination between homologs is disrupted in Brassica AAC allotriploids, a genomic configuration that may have facilitated the formation of rapeseed (Brassica napus L.) &#x223c;7,500&#x2005;years ago. Indeed, the presence of the haploid C genome induces supernumerary crossovers between homologous A chromosomes with dramatically reshaped distribution. However, the genetic mechanisms driving this phenomenon and their divergence between nascent and established lineages remain unclear. To address these concerns, we generated hybrids carrying additional C chromosomes derived either from an established lineage of the allotetraploid B. napus or from its diploid progenitor B. oleracea. We then assessed recombination variation across twelve populations by mapping male meiotic crossovers using single nucleotide polymorphism markers evenly distributed across the sequenced A genome. Our findings reveal that the C09 chromosome of B. oleracea is responsible for the formation of additional crossovers near pericentromeric regions. Interestingly, its counterpart from an established lineage of B. napus shows no significant effect on its own, despite having a similar content of meiotic genes. However, we showed that the B. napus C09 chromosome influences crossover formation through inter-chromosomal epistatic interactions with other specific C chromosomes. These results provide new insights into the genetic regulation of homologous recombination in Brassica and emphasize the role of genomic divergence since the formation of the allopolyploid B. napus.

Meiosis↗

Evolutionary conservation of ten microsatellite loci in four species of Felidae.

Short tandem repeat polymorphisms (STRP), or microsatellites, are widespread among vertebrate genomes and are useful in gene mapping and population studies due to a high level of length polymorphism. We describe here the isolation, characterization, and PCR amplification of 10 microsatellite loci from the domestic cat, Felis catus. The flanking primer sequences were conserved among other Felidae species, and amplification products demonstrated abundant polymorphism in puma, lion, cheetah, and domestic cat. The cheetah sample exhibited the lowest level of polymorphism for these loci among felid species.

Animals↗

Restricted diffusion and stability of carbachol-fluorescent nanospheres in-vivo.

Mapping neuronal populations that induce behavioral state changes after pharmacological activation requires discrete localization of drug injection sites, and is limited by widespread diffusion of molecular drugs. Nanospheres with diameters of 50-100 nm can reduce diffusion significantly because of their relatively large sizes. The cholinergic agonist carbachol was radiolabeled with methyl14C and incorporated within a latex nanosphere delivery system (LNDS). We quantitatively compared diffusion of 14C-carbachol within these nanospheres with that of free 14C-carbachol, demonstrating approximately ten-fold reduced radial diffusion by nanospheres 10 min to 24 h post-injection; approximately 90% of injected radioactivity was restricted to regions within approximately 100-150 microns and 1400-1500 microns respectively. Thus, incorporation of active agents such as drugs within nanospheres dramatically increases the precision of their delivery in-vivo (here about 1,000-fold by volume).

Animals↗

North American Indian cirrhosis in children: a review of 30 cases.

BACKGROUND: North American Indian childhood cirrhosis (NAIC) is a distinct, rapidly evolving form of familial cholestasis found in aboriginal children from northwestern Quebec. This is a retrospective review of the 30 patients treated in Quebec since the discovery of NAIC in 1970. METHODS: The clinical records and histologic samples from 30 patients were reviewed. Extensive metabolic, biochemical, viral, genetic, and radiologic studies were performed in most patients. RESULTS: Genetic analysis suggests autosomal recessive inheritance and a carrier frequency of 10% in this population. Gene mapping studies showed that the NAIC gene is located on chromosome 16q22. Typically, patients have neonatal cholestatic jaundice (70%) or hepatosplenomegaly (20%) with resolution of clinical jaundice by age 1 year but persistent direct hyperbilirubinemia. Portal hypertension was documented in 29 patients (91%). Variceal bleeding (15 patients, 50%) occurred as early as age 10 months. Surgical portosystemic shunting was performed in 13 of these 15 patients (87%); 4 (31%) rebled after 1 to 5 years. Fourteen patients died (47%). In 10 (71%), liver disease was the cause. Four children died of liver failure before liver transplantation became available. In transplanted livers, no recurrence of NAIC was observed after 1 to 10 years. Recognized infectious, metabolic, toxic, autoimmune, and obstructive causes of cirrhosis have been eliminated. The histologic features of NAIC show early bile duct proliferation and rapid development of portal fibrosis and biliary cirrhosis, suggesting a cholangiopathic phenomenon. CONCLUSION: Together with gene mapping studies showing that the NAIC gene is different from those of other familial cholestases, these observations suggest that NAIC is a distinct entity that could be classified as "progressive familial cholangiopathy."

Adolescent↗

Digital imaging colposcopy: corrected area measurements using shape-from-shading.

The quantitative measurement of areas on the cervix is of interest to researchers studying the natural history of human papilloma viral lesions. Measurement of areas from images obtained through a colposcope are, however, inherently in error due to the image being a two-dimensional projection of a three-dimensional object. The ability to correct for these errors through use of digital imaging colposcopy and a practical application of a shape from shading algorithm was developed in this study. The shape from shading technique requires empirical measurement of the relationship between observed light intensity and the viewing angle (referred to as a reflection map). It was found that a population mean reflection map provided a correction that was about as accurate as using an individual's own reflection map (making it unnecessary to measure a map for each exam). Digital red filtering of the images increased accuracy and precision of measurement.

Adolescent↗

Medical education in action: community-based experience and service in Nigeria.

Problem-based, student-centred learning at the Faculty of Health Sciences, Unilorin, Nigeria were incorporated in the overall objectives of producing students with a sense of service and a strong inclination toward broad community care and preventive medicine. The educational programme reflecting this concept was called COBES (community-based experience and service). Twice a year groups of between seven and fourteen students, each accompanied by two to three staff members, settled in a village or other community for 1 month. According to the Faculty's objectives, each group assessed the size of its community (population, areal map) at first. Malnutrition and infectious diseases were selected as the two health problems which were to be studied in depth during the first two COBES placements. Data were collected and analysed by the students from which deductions were made, and at the end of the placement a written report was required by the Faculty. Three learning situations and the experience gained from them by one group of students are reported: (1) What was our community? (2) The nutritional status of children, and (3) Guinea-worm infection. The educational benefits of the programme are discussed and the view of the students is brought out. A correct assessment of students' performances proved difficult. Other problems were related to the experimental situation of COBES, such as insufficient support of the programme by some staff members, the lack of programme structure and logistical shortcomings. The COBES programme, however, set a pattern of medical education which specifically suits Nigerian needs and probably those of other African countries.

Child↗

Fts insertional mutant of Salmonella typhimurium.

A temperature-sensitive filamentation (fts) Salmonella typhimurium mutant was isolated after transposon mutagenesis with mini-Tn 10dTc. The mutant was unable to form colonies after 20 h incubation at 37 degrees C on LB agar. Colonies appeared, however, after longer incubation at the restrictive temperature. Filamentation affected only part of the bacterial population. Rapid mapping using Mu dP22 hybrid phages revealed that the mutation, ftsD220, lies within minutes 68.5 and 73.6 on the genetic map. Further analysis revealed that the ftsD220 mapped at min 73 and that it is linked to cysG (6%) and to aroB (39%). Complementation tests suggested that the ftsD220 mutation is not homologous to a Escherichia coli ftsH mutation.

Chromosome Mapping↗

Identification and characterization of recD, a gene affecting plasmid maintenance and recombination in Escherichia coli.

We isolated mutations that reduce plasmid stability in dividing cell populations and mapped these mutations to a previously undescribed gene, recD, that affects recombination frequency and consequently the formation of plasmid concatemers. Insertions of the transposable element Tn10 into recD resulted in increased concatemerization and loss of pSC101 and ColE1-like replicons during nonselective growth. Both concatemer formation and plasmid instability in recD mutants require a functional recA gene. Mutations in recD are recessive to recD+ and map to a small region of the Escherichia coli chromosome located between recB and argA. Although the recD locus is distinct from loci encoding the two previously identified subunits of the RecBC enzyme, mutations in recD appear to affect the exonuclease activity of this enzyme.

Chromosome Mapping↗

Heterologous nuclear and chloroplast microsatellite amplification and variation in tea, Camellia sinensis.

The advantage of the cross transferability of heterologous chloroplast and nuclear microsatellite primers was taken to detect polymorphism among 24 tea (Camellia sinensis (L.) O. Kuntze) genotypes, including both the assamica and the sinensis varieties. Primer information was obtained from the closely related Camellia japonica species for four nuclear microsatellites, and from Nicotiana tabaccum for seven universal chloroplast microsatellites. All of the nuclear microsatellite loci tested generated an expected DNA fragment in tea, revealing between three and five alleles per locus. Four out of the seven chloroplast microsatellites primers amplified positively, and of these only one was polymorphic with three alleles, which is in agreement with the conserved nature of chloroplast microsatellites at the intraspecific level. A factorial correspondence analysis carried out on all genotypes and nuclear microsatellite alleles separated the assamica and sinensis genotypes into two groups, thus demonstrating the value of these markers in establishing the genetic relationship between tea varieties. Genetic diversity measured with nuclear microsatellites was higher than that measured with other types of molecular markers, offering prospects for their use in fingerprinting, mapping, and population genetic studies, whereas polymorphisms detected at a cpSSR locus will allow the determination of plastid inheritance in the species.

Base Sequence↗

Characterization of microsatellite markers in eastern white pine.

An enrichment cloning method was evaluated for the isolation of microsatellite loci from eastern white pine and the resulting markers were examined for polymorphisms. A 200-fold enrichment was achieved for highly abundant (AC)n repeats, but for much less abundant (ACAG)n repeats an enrichment of only 20-fold was obtained. Using a single set of PCR conditions, 19 microsatellite loci were identified from 77 primer pairs evaluated. Genotyping of 16 (AC)n loci in 16 unrelated white pines from the north-central United States revealed an average of 5.4 alleles per locus and an average observed heterozygosity of 0.515. Five loci were scored among megagametophytes from a single pine to obtain a haploid genotype of the segregating female meiotic products. All loci segregated according to Mendelian expectations and linkage was established for two of the loci. It was concluded that (AC)n loci are highly variable in this species and that SSR (simple sequence repeat) markers can be efficiently developed for genome mapping and population genetics studies.

Alleles↗

Responses of neurons in the medial superior temporal visual area to apparent motion stimuli in macaque monkeys.

Monkeys fixated a stationary spot during presentation of dot textures that moved in apparent motion defined by the spatial and temporal separations, Deltax and Deltat, between successive flashes of each dot. For each neuron, we assessed the speed tuning for smooth motion (Deltat = 2 or 4 ms) at speeds < or =128 degrees /s and the effect of varying the value of Deltat at speeds of 16 and 32 degrees /s. Many medial superior temporal (MST) neurons, like middle temporal (MT) neurons, were tuned for the speed of smooth motion and showed decreases in firing rate as the value of Deltat increased at a constant speed. A subset of MST neurons, however, showed monotonically increasing firing rates as a function of smooth stimulus speed and responses to apparent motion that paralleled a previously discovered illusion where estimates of target speed increase with the value of Deltat. Opponent firing rate, defined as the difference between responses for motion in the preferred and opposite directions, peaked at values of Deltat that were consistent with the behavioral illusion. Comparison with a new sample of MT neurons recorded with the same stimuli failed to reveal comparable effects. Attempts to map the population responses in MT and MST onto the behavioral illusion of increased speed succeeded by averaging the opponent response across MST neurons, but only by applying vector averaging to determine the preferred speed of the most active MT neurons. We suggest that a vector-averaging computation transforms MT's place code for target speed into the rate code of some MST neurons.

Action Potentials↗

Similarity in perception: a window to brain organization.

This paper presents a neural model of similarity perception in identification tasks. It is based on self-organizing maps and population coding and is examined through five different identification experiments. Simulating an identification task, the neural model generates a confusion matrix that can be compared directly with that of human subjects. The model achieves a fairly accurate match with the pertaining experimental data both during training and thereafter. To achieve this fit, we find that the entire activity in the network should decline while learning the identification task, and that the population encoding of the specific stimuli should become sparse as the network organizes. Our results, thus, suggest that a self-organizing neural model employing population coding can account for identification processing while suggesting computational constraints on the underlying cortical networks.

Brain↗

Tests for the replication of an association between Egfr and natural variation in Drosophila melanogaster wing morphology.

BACKGROUND: Quantitative differences between individuals stem from a combination of genetic and environmental factors, with the heritable variation being shaped by evolutionary forces. Drosophila wing shape has emerged as an attractive system for genetic dissection of multi-dimensional traits. We utilize several experimental genetic methods to validation of the contribution of several polymorphisms in the Epidermal growth factor receptor (Egfr) gene to wing shape and size, that were previously mapped in populations of Drosophila melanogaster from North Carolina (NC) and California (CA). This re-evaluation utilized different genetic testcrosses to generate heterozygous individuals with a variety of genetic backgrounds as well as sampling of new alleles from Kenyan stocks. RESULTS: Only one variant, in the Egfr promoter, had replicable effects in all new experiments. However, expanded genotyping of the initial sample of inbred lines rendered the association non-significant in the CA population, while it persisted in the NC sample, suggesting population specific modification of the quantitative trait nucleotide QTN effect. CONCLUSION: Dissection of quantitative trait variation to the nucleotide level can identify sites with replicable effects as small as one percent of the segregating genetic variation. However, the testcross approach to validate QTNs is both labor intensive and time-consuming, and is probably less useful than resampling of large independent sets of outbred individuals.

Animals↗