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PubMed1989

Declining trends in mortality from cerebrovascular disease at ages 10-65 years: a test of validity.

Recent reports of declining trends in mortality rates from cerebrovascular disease are based on underlying cause of death as stated on the death certificate, and may contain inaccuracies because death certificates are often completed without reference to all information in medical records, and because of changes in coding conventions and diagnostic fashion. This is a report of trends in mortality rates from cerebrovascular disease in Baltimore, Md., during 1950-1970 using data validated by reference to individual medical records from 19 hospitals. Overall accuracy of death certificate diagnoses did not change markedly during the study period. Death rates from subarachnoid hemorrhage increased in white women, but decreased in white men and in nonwhites of both sexes. Death rates from other cerebrovascular diseases declined in most sex and color groups, a result which cannot be attributed to errors in death certificate diagnoses. The increasing rates of subarachnoid hemorrhage observed in white women deserve further attention.

Adolescent↗

PubMed1983

The neural signal for skin indentation depth. I. Changing indentations.

Psychophysical tests on human subjects showed that judgments of skin indentation depth made when the fingertip was indented at rates from 0.2 to 16 mm/sec were quite insensitive to changes in indentation velocity. Similar results were obtained on the forearm at indentation velocities of 0.4 to 16 mm/sec. Recordings were made from mechanoreceptors in the monkey's hand that were able to respond over the same range of velocities and at comparable depths to determine how skin indentation depth might be signaled (coded) at the receptor level and to examine the rate sensitivity of the possible depth codes. It was found that most of the receptors with foci under the stimulator were recruited relatively early during an indentation, especially at velocities of 1.6 mm/sec and higher, making it improbable that the full range of indentation depths is signaled by the "subsurface" recruitment of different receptors at different indentation depths. A subsurface recruitment code involving subcutaneous receptors is not likely since subjects could feel virtually none of the stimuli after skin anesthesia. Progressive recruitment with depth of receptors whose foci lie further and further away from the stimulator ("lateral" recruitment) was considered an unlikely depth code because changing the area of the stimulator had little effect on its perceived depth. Also, it was shown that subjects could sense the curvature of the indentation (the profile of the depth at right angles to the skin surface), which requires information about the depth of individual patches of skin beneath the stimulator. There is no obvious way that a lateral recruitment code can provide this information. Thus it is probable that the discharge rate of some or all of the receptors excited by the indentation is involved in indicating its depth. Both impulse frequency and receptor recruitment at any given depth increased as the velocity of the indentation increased. The demonstrated reliability of information about skin indentation depth in humans indicates that the central neural circuitry responsible for judgments of skin indentation depth is able to compensate for the rate-sensitive receptor signals.

Adult↗

PubMed1981

Medicare program; availability of information and records to the public--Health Care Financing Administration. Final rule.

We are changing the Code of Federal Regulations (CFR) location of certain regulations applicable to the Medicare program that concern the availability of information and records to the public. Currently, HCFA shares regulations on that subject with the Social Security Administration (SSA) in Title 20 of the CFR. This change in location is one of a series intended to consolidate HCFA regulations in one place, Title 42 of the CFR, for the convenience of providers of services, intermediaries and others who use our regulations. This move will combine these regulations on the general availability of information with others in Title 42 on disclosure of official records and information about individuals. We do not intend any substantive changes. We have merely inserted updated addresses for requesting records, changed certain references to make them applicable to HCFA rather than SSA, and deleted obsolete items from the list of publications. Substantive changes will be proposed at a later date when we publish regulations on the availability of information and records for both the Medicare and Medicaid programs.

Aged↗

PubMed1998

Is there a neural code?

Rate coding and temporal coding are two extremes of the neural coding process. The concept of a stationary state corresponds to the information processing approach that views the brain as a decision maker, adopts rate coding as its main strategy and endorses the single- or few neuron approach. If information derived from sensory stimulation is used to continuously update the brain's internal representation of the world, then neural codes may change with time through learning. As a consequence, the same spike sequence may be interpreted differently (or evoke a different behavior) later in the day. This non-stationary viewpoint is embodied in the representational model of brain function that stresses learning and plasticity and employs temporal coding in neural assemblies. We argue that the switching between quasi-stable brain states as a result of learning is more relevant than the neuronal patterns, and the correlations between them, that are found during stationary states. The neural code likely resides in the activity patterns that cause this state-switching.

Animals↗

PubMed1999

Cancer mortality in Russia and Ukraine: validity, competing risks and cohort effects.

BACKGROUND: The dramatic increase in mortality in Russia and Ukraine in the late 1980s and 1990s has been due to increases in certain causes of death, particularly cardiovascular disease and accidents and violence. In contrast, there has been a slight fall in mortality from cancer. METHODS: This paper presents an analysis of trends and patterns in cancer mortality and examines four possible explanations for its recent fall: changes in data collection; cohort effects; competing mortality from other causes of death; and improvements in health care. RESULTS: All contribute to some extent to the observed changes, with each affecting predominantly different age groups. There is evidence of a significant underrecording of cancer deaths among the elderly especially in rural areas and of significant changes in coding practices in the early 1990s. Competing mortality from cardiovascular diseases and accidents can explain some reduction in male deaths from cancer in middle age. Birth cohort effects can explain some reduction among males after early middle age and among females at all ages. The impact of changes in health care are more difficult to identify with certainty but there is evidence of reduced deaths from childhood leukaemia. IMPLICATIONS: Recent changes in mortality in Russia are complex and their understanding will require a multidisciplinary approach embracing demography, epidemiology and health services research.

Adolescent↗

PubMed2000

Functional coupling shows stronger stimulus dependency for fast oscillations than for low-frequency components in striate cortex of awake monkey.

It has been argued that coupling among the neural signals activated by a visual object supports binding of local features into a coherent object perception. During visual stimulation by a grating texture we studied functional coupling by calculating spectral coherence among pairs of signals recorded in the striate cortex of awake monkeys. Multiple unit activity (MUA) and local field potentials (LFP, 1-140 Hz) were extracted from seven parallel broad band recordings. Spectral coherence was dominated by high-frequency oscillations in the range 35-50 Hz and often by additional low-frequency components (0-12 Hz). Functional coupling among separate cortical sites was more stimulus specific for MUA than for LFP: MUA coherence at high and low frequencies depended highly significantly on: (i) the similarity of the preferred orientations at the two sites - the more similar the higher the coherence; (ii) the orientation of the stimulus grating - with highest coherence at half angle between the preferred orientations at the two sites; (iii) cortical distance - coherence decreases to noise levels at approximately 3 mm (MUA) and 6 mm (LFP). Coherence of fast oscillations did not depend on the degree of coaxiality of the orientation-sensitive receptive fields, whereas low frequencies showed significant dependency. This indicates that different frequency components can engage different coupling networks in the striate cortex which probably support different coding tasks. Changes in average oscillation frequency with stimulus orientation were highly significant for fast oscillations while there was no dependency for low frequencies. Finally, stimulus-related spectral power and coherence of fast oscillations were considerably higher than of low frequency components. Fast oscillations may therefore contribute more to feature binding and coding of object continuity than low-frequency components, at least for texture surfaces as analysed here.

Animals↗

PubMedDate not supplied

Codes, operations, measurements and neural networks.

Numerous neural codes and primary neural operations (logical and arithmetical ones, mappings, transformations) were listed [e.g. Perkel, D., Bullock, T.H., 1968. Neurosci. Res. Program Bull 6, 221-348] during the past decades. None of them is ubiquitous or universal. In reality neural operations take place in continuous time and working with unreliable elements, but they still can be simulated with synchronized discrete time scales and chaotic models. Here, a possible neural mechanism, called 'measure like' code is introduced and examined. The neurons are regarded as measuring devices, dealing with 'measures', more or less in mathematical sense. The subadditivity--eminent property of measures--may be implemented with neuronal refractoriness and such synapses operate like particle counters with dead time. This hypothetical code is neither ubiquitous, nor universal, e.g. temporal summation (multiplication) causes just the opposite phenomenon, the supra-additivity also with respect to the number of spikes (anti-measures). This is a cause of more difficult neural implementation of OR gate, than that of the AND. Possibilities for transitional mechanisms (e.g. between traditional logical gates, etc.) are stressed here. Parameter tuning might change either code or operation.

Action Potentials↗

PubMed1988

Cloning of cDNA coding for carbamyl phosphate synthetase I and changes in levels of CPS1 mRNA during hepatocarcinogenesis.

cDNA coding for carbamyl phosphate synthetase I was cloned from recombinant plasmid with insert complementary to the mRNA for CPS1 followed by hybrid-selected translation screening. The length of the insert CPS1 cDNA was approximately 800 base pairs. Using this cDNA as a probe, it was found by dot-blot analysis of the total RNAs and poly(A)+-RNAs isolated from rat livers with different pathological lesions induced by diethylnitrosamine that the levels of CPS1 mRNA were decreased, the decrease being correlated with the malignancy of hepatocytes during carcinogenesis.

Animals↗

PubMed2004

Sensory re-education after nerve repair: aspects of timing.

The recovery of functional sensibility after nerve transection and repair is often disappointing. Here we address the timing of sensory re-education that aims at re-learning and modulating the changed sensory code from the hand after such an injury. Such training utilises the capacity for cortical functional re-modelling which characterises the young as well as the adult brain. Sensory re-education is traditionally not introduced until there is reinnervation in the hand, and such a late onset of training may be one explanatory factor for the poor functional results after nerve repair. Since functional reorganisation changes of the cortex occurring after changes in peripheral input are very fast processes, we suggest that this specific intervention should be introduced very early in the rehabilitation phase--already in the initial phase after nerve repair when no axons have yet arrived to the asensible hand. The goal is to avoid, minimise and modulate the central functional re-organisation which follows the de-afferentiation associated with nerve injury and repair. This early intervention can be done with the use of artificial sensibility the first post-operative day. According to this technique, based on sense substitution and utilising the multimodal capacity of the brain, miniature microphones on the fingertips of the asensible hand pick up the friction sound generated by active touch. The vibro-tactile signals are stereophonically transposed to vibro-acoustic signals, thereby providing an alternate feed-back which hypothetically helps to maintain or re-establish the cortical hand map.

Acoustic Stimulation↗

PubMed2001

Mutation of proline 409 to arginine in the meander region of cytochrome p450c17 causes severe 17 alpha-hydroxylase deficiency.

We elucidated the molecular basis of 17 alpha-hydroxylase deficiency in a Chinese patient with male pseudohermaphroditism. The patient is a compound heterozygote, carrying two different mutant alleles in the CYP17 gene. The first mutation, g.6333--6341delGACTCTTTCA, located in exon 8, was reported in a Thai patient living in a rural village in Thailand. We suggest that g.6333--6341delGACTCTTTCA may be a prevalent mutation causing P450c17 deficiency in Southeast Asia. The second mutation is a missense mutation, g.5582C>G, located in exon 7, changing the codon 409 from CCG to CGG, and changing the coded amino acid from proline to arginine, i.e., P409R. This proline residue is conserved in P450c17 of other species and other human P450 proteins. Site-directed mutagenesis, in vitro expression, and functional analysis of the P409R mutant in COS-1 cells show that it has a complete lack of 17 alpha-hydroxylase activity. The proline residue probably causes a turn in the meander region of P450c17, and we hypothesize, by comparison to homologous proteins, that the change in the protein conformation may abolish heme incorporation or may prevent P450c17 from interacting with electron donors.

Adolescent↗

PubMed2001

Consequences of Hox gene duplication in the vertebrates: an investigation of the zebrafish Hox paralogue group 1 genes.

As a result of a whole genome duplication event in the lineage leading to teleosts, the zebrafish has seven clusters of Hox patterning genes, rather than four, as described for tetrapod vertebrates. To investigate the consequences of this genome duplication, we have carried out a detailed comparison of genes from a single Hox paralogue group, paralogue group (PG) 1. We have analyzed the sequences, expression patterns and potential functions of all four of the zebrafish PG1 Hox genes, and compared our data with that available for the three mouse genes. As the basic functions of Hox genes appear to be tightly constrained, comparison with mouse data has allowed us to identify specific changes in the developmental roles of Hox genes that have occurred during vertebrate evolution. We have found variation in expression patterns, amino acid sequences within functional domains, and potential gene functions both within the PG1 genes of zebrafish, and in comparison to mouse PG1 genes. We observed novel expression patterns in the midbrain, such that zebrafish hoxa1a and hoxc1a are expressed anterior to the domain traditionally thought to be under Hox patterning control. The hoxc1a gene shows significant coding sequence changes in known functional domains, which correlate with a reduced capacity to cause posteriorizing transformations. Moreover, the hoxb1 duplicate genes have differing functional capacities, suggesting divergence after duplication. We also find that an intriguing function 'shuffling' between paralogues has occurred, such that one of the zebrafish hoxb1 duplicates, hoxb1b, performs the role in hindbrain patterning played in mouse by the non-orthologous Hoxa1 gene.

Amino Acid Sequence↗

PubMed1996

Missense mutation in the pore region of HERG causes familial long QT syndrome.

BACKGROUND: Long QT syndrome (LQT) is an inherited cardiac disorder that results in syncope, seizures, and sudden death. In a family with LQT, we identified a novel mutation in human ether-a-go-go-related gene (HERG), a voltage-gated potassium channel. METHODS AND RESULTS: We used DNA sequence analysis, restriction enzyme digestion analysis, and allele-specific oligonucleotide hybridization to identify the HERG mutation. A single nucleotide substitution of thymidine to guanine (T1961G) changed the coding sense of HERG from isoleucine to arginine (Ile593Arg) in the channel pore region. The mutation was present in all affected family members; the mutation was not present in unaffected family members or in 100 normal, unrelated individuals. CONCLUSIONS: We conclude that the Ile593Arg missense mutation in HERG is the cause of LQT in this family because it segregates with disease, its presence was confirmed in three ways, and it is not found in normal individuals. The Ile593Arg mutation may result in a change in potassium selectivity and permeability leading to a loss of HERG function, thereby resulting in LQT.

Base Sequence↗

PubMed2006

Founder effect, plant host, and recombination shape the emergent population of begomoviruses that cause the tomato yellow leaf curl disease in the Mediterranean basin.

Tomato yellow leaf curl disease (TYLCD)-associated viruses present a highly structured population in the western Mediterranean basin, depending on host, geographical region and time. About 1,900 tomato and common bean samples were analyzed from which 111 isolates were characterized genetically based on a genome sequence that comprises coding and non-coding regions. Isolates of three distinct begomoviruses previously described were found (Tomato yellow leaf curl virus, TYLCV, Tomato yellow leaf curl Sardinia virus, TYLCSV, and Tomato yellow leaf curl Málaga virus, TYLCMalV), together with a novel recombinant virus. Mixed infections were detected in single plants, rationalizing the occurrence of recombinants. Except for TYLCV-type strain, single, undifferentiated subpopulations were present for each virus type, probably the result of founder effects. Limited genetic variation was observed in genomic regions, with selection against amino acid change in coding regions.

Begomovirus↗

PubMed2003

Multiple-cause coding of death from myocardial infarction: population-based study of trends in death certificate data.

BACKGROUND: Data on long-term trends in mortality are generally unavailable for multiple-cause coding of deaths. We wanted to know whether multiple-cause coding of deaths for myocardial infarction contributes much to the interpretation of death certificate data on mortality rates for this condition. METHODS: We analysed all causes of death on death certificates in the former Oxford health service region from 1979 to 1998. RESULTS: Of 69,333 death certificates that included myocardial infarction as a cause of death, it was the underlying cause of death in 93.6 per cent. The ratio of 'mentions' to 'underlying cause' was broadly similar over the study period, during which time there were substantial falls in mortality rates. There were significant changes to the ratios, associated with timing of changes to coding rules; but their effects were small. The ratio of mentions to underlying cause was similar in men and women and in different age groups. CONCLUSION: The underlying cause of death was a robust and almost complete measure of certified deaths for myocardial infarction.

Adult↗

PubMed2006

Ets2 binding site single nucleotide polymorphism at the hTERT gene promoter--effect on telomerase expression and telomere length maintenance in non-small cell lung cancer.

The aim of this study was to elucidate the occurrence of DNA sequence changes in the promoter region of hTERT gene, and its effect on telomerase expression and telomere length maintenance in non-small cell lung cancer (NSCLC). Between January 2002 and December 2003, 66 NSCLC patients were studied. The expression of hTERT, telomerase activity (TA), and c-Myc were examined, and the terminal restriction fragment length (TRFL) was measured. A t/n-TRFLR was obtained by dividing the TRFL of the tumour tissue by TRFL of the paired normal tissue. PCR products were sequenced and compared with known hTERT gene promoter sequence for a length of 716 bp upstream of the transcription starting code. The changes of any known sequence and/or c-Myc expression with their impact on telomerase activity and TRFL maintenance were measured. Positive hTERT, TA and c-Myc expression was observed in 43 (65.2%), 39 (59.1%) and 59 (89.4%) of the tumour tissue samples, respectively. Except for one patient who had C/C (in normal tissue) homozygotes to T/C (in tumour tissue) heterozygotes point mutation, a novel single nucleotide polymorphism (SNP) -245 kb upstream (Ets2 binding site) of the hTERT gene was observed in all normal and tumour tissues, including C/C in 9, T/C in 35, and T/T in 22 of the tumour tissues. The TA of C/C homozygotes was lower than that of T/T homozygotes (P=0.0331), while the t/n-TRFLR of C/C homozygotes was higher than that of T/T homozygotes (P=0.0621). The latter was even more obvious when c-Myc were positive (P=0.0185). Our data shows that T/T homozygotes have a lower t/n-TRFLR, but a stronger TA expression, suggesting that the studied Ets2 binding site is a positive regulator of hTERT gene. SNP may interfere with Ets2 binding and lower TA expression in T/C heterozygotes and C/C homozygotes.

Aged↗

PubMedDate not supplied

Worldwide trends in asthma mortality.

Statistics for deaths from asthma yield widely variable mortality rates between countries. Validation studies show significant inaccuracies in certification of cause of death in older subjects, and probable underreporting of asthma deaths in some countries, explaining some of the international differences noted. The introduction of the ninth revision of the World Health Organisation International Classification of Diseases brought a step increase in reported asthma mortality rates in 1979, but the last decade has seen a gradual increase in mortality rates in many countries, especially in young people, not explained by this change in code. Diagnostic transfer does not adequately explain these increases. Individuals at risk of death from asthma are more likely to be non-caucasian, non-compliant, and young, with a history of previous life-threatening episodes, hospital admissions, and precipitous attacks. Studies of circumstances of death have emphasized overreliance on beta-agonists and underuse of corticosteroids as two primary deficiencies in management, but there remains debate about the causality of the association between increased asthma mortality and increased usage of beta-agonists. The gradual increase in asthma mortality seen in New Zealand over the last 40 years, with episodic increases in the rising baseline, together with similar but more gradual changes in other countries, raises concerns about whether current treatment practices may adversely affect asthma severity and mortality. Further studies are required to validate asthma mortality statistics, and to establish causation of deaths.

Adolescent↗

PubMed1996

Primary cortical representation of sounds by the coordination of action-potential timing.

Cortical population coding could in principle rely on either the mean rate of neuronal action potentials, or the relative timing of action potentials, or both. When a single sensory stimulus drives many neurons to fire at elevated rates, the spikes of these neurons become tightly synchronized, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept. Here we demonstrate that the relative timing of cortical action potentials can signal stimulus features themselves, a function even more basic than feature grouping. Populations of neurons in the primary auditory cortex can coordinate the relative timing of their action potentials such that spikes occur closer together in time during continuous stimuli. In this way cortical neurons can signal stimuli even when their firing rates do not change. Population coding based on relative spike timing can systemically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

Action Potentials↗

PubMed2000

Comparative genomics of mitochondrial DNA in members of the Drosophila melanogaster subgroup.

In this study, a comparative genomics approach is employed to investigate the forces that shape evolutionary change in the mitochondrial DNA (mtDNA) of members of the Drosophila melanogaster subgroup. This approach facilitates differentiation of the patterns of variation resulting from processes acting at a higher level from those acting on a single gene. The mitochondrial genomes of three isofemale lines of D. simulans (siI, -II, and -III), two of D. melanogaster (Oregon R and a line from Zimbabwe), and D. mauritiana (maI and -II), and one of D. sechellia were sequenced and compared with that derived from D. yakuba. Data presented here indicate that at least three broad mechanisms shape the evolutionary dynamics of mtDNA in these taxa. The first set of mechanisms is intrinsic to the molecule. Dominant processes may be interpreted as selection for an increased rate of replication of the mtDNA molecule, biases in DNA repair, and differences in the pattern of nucleotide substitution among strands. In the genes encoded on the major strand (62% of the coding DNA) changes to or from C predominate, whereas on the minor changes to or from G predominate. The second set of mechanisms affects distinct lineages. There are evolutionary rate differences among lineages, possibly owing to population demographic changes or changes in mutational biases. This is supported by the heterogeneity found in synonymous, nonsynonymous, and silent substitutions. The third set of mechanisms differentially affects distinct genes. A maximum-likelihood sliding-window analysis detected four disjunct regions that have a significantly different nucleotide substitution process from that derived from the complete sequence. These data show the potential for comparative genomics to tease apart subtle forces that shape the evolution of DNA.

Animals↗