SEARCH · PubMed Health

Results for “threshold model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMedDate not supplied

The peripheral hearing mechanism: a biochemical and biological approach.

A new approach is described to the problem or hearing at energy levels near threshold. Models depending on the macro-physics of levers are rejected. Instead, evidence is presented for frequency analysis, signal placement and energy transduction by the properties (known or experimentally determined) or the cochlea and of the structures within the scala media. The hypothesis developed rests on the established theorems of Gabor and Brillouin, and at the same time is based on the data of enzymology. Care is taken not only that the hypothesis does not conflict but that it is actually consonant with recent solid state physics. The cochlea by virtue of its internal geometry and contained column of fluid is considered to perform a Fourier analysis to a first approximation. This crude "placement" of the acoustic signal is refined by the semi-solid-state lattice of the tectorial membrane which far from permitting dissipation of the signal energy actually "concentrates" the energy at the membrane surface of the hair processes of a hair cell. Here biochemical transduction, akin to the processes known for other sensory cells, transforms acoustic energy through an ion-shuttling mechanism to the form of energy characteristic of living cells, viz. enzyme conformational changes.

Cochlea↗

PubMed1994

Alzheimer's residents' cognitive and functional measures: special and traditional care unit comparison.

The aim of this field experiment was to compare the effects of a special care unit (SCU) on residents with Alzheimer's disease (AD) who lived on the SCU and on traditional (integrated) nursing home units. Twenty-two subjects, 13 on the SCU and 9 on traditional integrated units were compared. Repeated measures ANOVA was used to assess differences between the two groups and within the groups over two bimonthly pretests and two bimonthly posttests. No significant differences on cognitive or functional abilities scores were evident for the groups and no significant differences were found over time. However, consistent with the prediction of the Progressively Lower Stress Threshold Model, the SCU subjects' function was better than subjects on traditional units when measured by socially accessible behaviors.

Activities of Daily Living↗

PubMed1998

Probable reasons for expressed agitation in persons with dementia.

Nursing home patients with dementia were videotaped in three previous studies. Sixty sequences of nine patients exhibiting agitated behaviors were examined to identify the most probable antecedents to agitation. Probable reasons were interpreted and applied to the Progressively Lowered Stress Threshold model, which suggests that agitation is stress related. Analysis suggests that agitation often serves as a form of communication. Two underlying reasons seem to be that the patient had loss of control over the situation and deficient autonomy. The most common causes for expressed agitation were interpreted as discomfort, a wish to be served immediately, conflict between patients or with nursing staff, reactions to environmental noises or sound, and invasion of personal space. It is recommended that nursing staff promote autonomy and independency for this group of patients whenever possible. By evaluating probable reasons for expressed agitation, the nursing staff can take steps to prevent or alleviate agitation.

Aged↗

PubMedDate not supplied

Sources of variation and genetic profile of spontaneous, out-of-season ovulatory activity in the Chios sheep.

Organising the breeding plan of a seasonally breeding species, such as sheep, presents a challenge to farmers and the industry as a whole, since both economical and biological considerations need to be carefully balanced. Understanding the breeding activity of individual animals becomes a prerequisite for a successful breeding program. This study set out to investigate the sources of variation and the genetic profile of the spontaneous, out-of-season ovulatory activity of ewes of the Chios dairy sheep breed in Greece. The definition of the trait was based on blood progesterone levels, measured before exposing the ewes to rams, which marks the onset of the usual breeding season. Data were 707 records, taken over two consecutive years, of 435 ewes kept at the Agricultural Research Station of Chalkidiki in northern Greece. When all available pedigree was included, the total number of animals involved was 1068. On average, 29% of all ewes exhibited spontaneous, out-of-season ovulatory activity, with no substantial variation between the years. Significant sources of systematic variation were the ewe age and live weight, and the month of previous lambing. Older, heavier ewes, that had lambed early the previous autumn, exhibited more frequent activity. Heritability estimates were 0.216 (+/-0.084) with a linear and 0.291 with a threshold model. The latter better accounts for the categorical nature of the trait. The linear model repeatability was 0.230 (+/-0.095). The results obtained in this study support the notion that spontaneous out-of-season ovulatory activity can be considered in the development of a breeding plan for the Chios sheep breed.

Animals↗

PubMed2005

Two novel quantitative trait linkage analysis statistics based on the posterior probability of linkage: application to the COGA families.

BACKGROUND: In this paper we apply two novel quantitative trait linkage statistics based on the posterior probability of linkage (PPL) to chromosome 4 from the GAW 14 COGA dataset. Our approaches are advantageous since they use the full likelihood, use full phenotypic information, do not assume normality at the population level or require population/sample parameter estimates; and like other forms of the PPL, they are specifically tailored to accumulate linkage evidence, either for or against linkage, across multiple sets of heterogeneous data. RESULTS: The first statistic uses all quantitative trait (QT) information from the pedigree (QT-posterior probability of linkage, PPL); we applied the QT-PPL to the trait ecb21 (resting electroencephalogram). The second statistic allows simultaneous incorporation of dichotomous trait data into the QT analysis via a threshold model (QTT-PPL); we applied the QTT-PPL to combined data on ecb21 and ALDX1. We obtained a QT-PPL of 96% at GABRB1 and a QT-PPL of 18% at FABP2 while the QTT-PPL was 4% and 2% at the same two loci, respectively. By comparison, the variance-components (VC) method, as implemented in SOLAR, yielded multipoint VC LOD scores of 2.05 and 2.21 at GABRB1 and FABP2, respectively; no other VC LODs were greater than 2. CONCLUSION: The QTT-PPL was only 4% at GABARB1, which might suggest that the underlying ecb21 gene does not also cause ALDX1, although features of the data complicate interpretation of this result.

Alcoholism↗

PubMed2005

Prevalence of physical and verbal aggressive behaviours and associated factors among older adults in long-term care facilities.

BACKGROUND: Verbal and physical aggressive behaviours are among the most disturbing and distressing behaviours displayed by older patients in long-term care facilities. Aggressive behaviour (AB) is often the reason for using physical or chemical restraints with nursing home residents and is a major concern for caregivers. AB is associated with increased health care costs due to staff turnover and absenteeism. METHODS: The goals of this secondary analysis of a cross-sectional study are to determine the prevalence of verbal and physical aggressive behaviours and to identify associated factors among older adults in long-term care facilities in the Quebec City area (n = 2,332). RESULTS: The same percentage of older adults displayed physical aggressive behaviour (21.2%) or verbal aggressive behaviour (21.5%), whereas 11.2% displayed both types of aggressive behaviour. Factors associated with aggressive behaviour (both verbal and physical) were male gender, neuroleptic drug use, mild and severe cognitive impairment, insomnia, psychological distress, and physical restraints. Factors associated with physical aggressive behaviour were older age, male gender, neuroleptic drug use, mild or severe cognitive impairment, insomnia and psychological distress. Finally, factors associated with verbal aggressive behaviour were benzodiazepine and neuroleptic drug use, functional dependency, mild or severe cognitive impairment and insomnia. CONCLUSION: Cognitive impairment severity is the most significant predisposing factor for aggressive behaviour among older adults in long-term care facilities in the Quebec City area. Physical and chemical restraints were also significantly associated with AB. Based on these results, we suggest that caregivers should provide care to older adults with AB using approaches such as the progressively lowered stress threshold model and reactance theory which stress the importance of paying attention to the severity of cognitive impairment and avoiding the use of chemical or physical restraints.

Aged↗

PubMed2005

Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response.

We discuss the similarities and differences of two types of effects that occur at low but not high doses of chemicals: hormesis and stimulation by oestrogenic endocrine-disrupting chemicals or xenoestrogens. While hormesis is a general phenomenon evoked by many compounds, oestrogenic stimulation occurs for specific chemicals that disrupt actions of endogenous oestrogen. Both types of phenomena can induce an inverted-U dose-response curve, resulting from low-dose stimulation of response, and thus challenge current methods of risk assessment. Hormesis is generally thought to be caused by an over-reaction of detoxification mechanisms, which is considered an adaptive response that should protect an organism from subsequent stress. One view of the hormetic low-dose stimulatory response, i.e., increased performance, is that it is beneficial. In contrast, we propose that for manmade xenoestrogens this is never the case. This is demonstrated with examples for low doses of the oestrogenic environmental chemicals bisphenol A and octylphenol, and the oestrogenic drug diethylstilbestrol. Adverse low-dose effects include oviduct rupture, an enlarged prostate, feminization of males and reduced sperm quality. These adverse stimulatory effects divert energy needed for other processes, resulting in reduced fitness. In conclusion, while there are similarities (inverted-U dose-response), there are also differences, adaptive response for hormesis versus adverse stimulatory response for low doses of manmade xenoestrogens, that have been almost totally ignored in discussions of hormesis. We propose that the risk posed by low doses of manmade xenoestrogens that show inverted-U dose-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.

Animals↗

PubMed2001

Examining the comorbidity of ADHD-related behaviours and conduct problems using a twin study design.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD) frequently co-occur, the underlying mechanisms for this comorbidity are not well understood. AIMS: To examine whether ADHD and conduct problems share common risk factors and whether ADHD+CD is a more heritable variant of ADHD. METHOD: Questionnaires were sent to 2846 families. Parent-rated data were obtained for 2082 twin pairs and analysed using bivariate genetic analysis and a liability threshold model approach. RESULTS: The overlap of ADHD and conduct problems was explained by common genetic and non-shared environmental factors influencing both categories. Nevertheless, the two categories appeared to be partly distinct in that additional environmental factors influenced conduct problems. It appeared that ADHD+CD was a genetically more severe variant of ADHD. CONCLUSIONS: Conduct problems and ADHD share a common genetic aetiology; ADHD+CD appears to be a more severe subtype in terms of genetic loading as well as clinical severity.

Adolescent↗

PubMed1984

Congenital taillessness in AGUS inbred rats.

From a survey of breeding records of the AGUS/ Lac rat colony, 1% of animals weaned were found to lack tails. Post-mortem examination of 5 females showed major skeletal and genital abnormalities. Tailless rats were found more often than expected in 4th and 5th litters. A 'threshold' model of inheritance was postulated with an unknown environmental factor 'triggering' the condition.

Animals↗

PubMed2003

Selection strategies for linkage studies using twins.

Genetic linkage analysis for complex diseases offers a major challenge to geneticists. In these complex diseases multiple genetic loci are responsible for the disease and they may vary in the size of their contribution; the effect of any single one of them is likely to be small. In many situations, like in extensive twin registries, trait values have been recorded for a large number of individuals, and preliminary studies have revealed summary measures for those traits, like mean, variance and components of variance, including heritability. Given the small effect size, a random sample of twins will require a prohibitively large sample size. It is well known that selective sampling is far more efficient in terms of genotyping effort. In this paper we derive easy expressions for the information contributed by sib pairs for the detection of linkage to a quantitative trait locus (QTL). We consider random samples as well as samples of sib pairs selected on the basis of their trait values. These expressions can be rapidly computed and do not involve simulation. We extend our results for quantitative traits to dichotomous traits using the concept of a liability threshold model. We present tables with required sample sizes for height, insulin levels and migraine, three of the traits studied in the GenomEUtwin project.

Genetic Linkage↗

PubMed2004

Genetic influences in self-reported symptoms of obstructive sleep apnoea and restless legs: a twin study.

Sleep disorders, such as obstructive sleep apnoea (OSA) and restless legs syndrome (RLS), are very common. The relative importance of genetic and nongenetic (environmental) influences on the symptomatology of these conditions has not been well studied. This study uses the twin design to examine this by evaluating OSA and RLS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. Six thousand six hundred unselected female twin pairs, identified from a national volunteer twin register, were asked to complete a medical questionnaire. This questionnaire included questions on OSA and RLS symptoms, as well as questions on subject demographics, past medical history, smoking history and menopausal status. Responses were obtained from 4503 individuals (68% response rate). A total of 1937 twin pairs were evaluable: 933 MZ pairs (mean [range] age 51 [20-76] years) and 1004 DZ pairs (age 51 [20-80] years). Concordance rates were higher for MZ than DZ twins for OSA and RLS symptoms. Multifactorial liability threshold modeling suggests that additive genetic effects combined with unique environmental factors provide the best model for OSA and RLS symptoms. Heritability was estimated to be 52% (95% confidence interval 36% to 68%) for disruptive snoring, 48% (37% to 58%) for daytime sleepiness, 54% (44% to 63%) for restless legs, and 60% (51% to 69%) for legs jerking. These estimates dropped only slightly after adjustment for potential confounding influences on the symptoms of snoring and daytime sleepiness. These results suggest a substantial genetic contribution to the symptomatology of OSA and RLS. More research is needed to identify the genes responsible, and may ultimately lead to new therapies.

Adult↗

PubMed1991

A population-based study of bronchial asthma in adult twin pairs.

Aggregation of cases of bronchial asthma in adult twin pairs was studied in the nationwide Finnish twin cohort consisting of 13,888 adult monozygotic (MZ) and same-sex dizygotic (DZ) pairs. Cases of asthma were ascertained by record-linkage from three sources of data: death certificates from the Central Statistical Office; hospital discharges from the nationwide hospital registry; and the nationwide registry for fully reimbursed medications of the Social Insurance Institution. A diagnosis of bronchial asthma in one or more of these registers was obtained for 525 (236 men and 289 women) out of 27,776 twin individuals. Among MZ pairs, ten concordant and 138 discordant pairs were identified, while among DZ pairs, 12 concordant and 343 discordant pairs were found. In the whole sample the observed-expected ratio for the number of pairs concordant for bronchial asthma was 4.30 (95 percent confidence interval [CI], 2.06 to 7.90) in MZ pairs and 2.61 (95 percent CI, 1.35 to 4.56) in DZ pairs. Using a multifactorial threshold model, we estimated the correlation in liability to asthma as 0.425 (SE = 0.07) in MZ twins and 0.247 (SE = 0.06) in DZ twins, and we obtained a heritability estimate of 35.6 percent. The data also showed a gender difference in asthma heredity, which may, however, be due to chance events affecting the distribution of concordant pairs.

Adult↗

PubMed2005

Evidence of a major gene from Bayesian segregation analyses of liability to osteochondral diseases in pigs.

Bayesian segregation analyses were used to investigate the mode of inheritance of osteochondral lesions (osteochondrosis, OC) in pigs. Data consisted of 1163 animals with OC and their pedigrees included 2891 animals. Mixed-inheritance threshold models (MITM) and several variants of MITM, in conjunction with Markov chain Monte Carlo methods, were developed for the analysis of these (categorical) data. Results showed major genes with significant and substantially higher variances (range 1.384-37.81), compared to the polygenic variance (sigmau2). Consequently, heritabilities for a mixed inheritance (range 0.65-0.90) were much higher than the heritabilities from the polygenes. Disease allele frequencies range was 0.38-0.88. Additional analyses estimating the transmission probabilities of the major gene showed clear evidence for Mendelian segregation of a major gene affecting osteochondrosis. The variants, MITM with informative prior on sigmau2, showed significant improvement in marginal distributions and accuracy of parameters. MITM with a "reduced polygenic model" for parameterization of polygenic effects avoided convergence problems and poor mixing encountered in an "individual polygenic model." In all cases, "shrinkage estimators" for fixed effects avoided unidentifiability for these parameters. The mixed-inheritance linear model (MILM) was also applied to all OC lesions and compared with the MITM. This is the first study to report evidence of major genes for osteochondral lesions in pigs; these results may also form a basis for underpinning the genetic inheritance of this disease in other animals as well as in humans.

Animals↗

PubMed2006

Multiple-interval mapping for ordinal traits.

Many statistical methods have been developed to map multiple quantitative trait loci (QTL) in experimental cross populations. Among these methods, multiple-interval mapping (MIM) can map QTL with epistasis simultaneously. However, the previous implementation of MIM is for continuously distributed traits. In this study we extend MIM to ordinal traits on the basis of a threshold model. The method inherits the properties and advantages of MIM and can fit a model of multiple QTL effects and epistasis on the underlying liability score. We study a number of statistical issues associated with the method, such as the efficiency and stability of maximization and model selection. We also use computer simulation to study the performance of the method and compare it to other alternative approaches. The method has been implemented in QTL Cartographer to facilitate its general usage for QTL mapping data analysis on binary and ordinal traits.

Algorithms↗

PubMed2006

The effect of dose rate on radiation-induced neoplastic transformation in vitro by low doses of low-LET radiation.

The dependence of the incidence of radiation-induced cancer on the dose rate of the radiation exposure is a question of considerable importance to the estimation of risk of cancer induction by low-dose-rate radiation. Currently a dose and dose-rate effectiveness factor (DDREF) is used to convert high-dose-rate risk estimates to low dose rates. In this study, the end point of neoplastic transformation in vitro has been used to explore this question. It has been shown previously that for low doses of low-LET radiation delivered at high dose rates, there is a suppression of neoplastic transformation frequency at doses less than around 100 mGy. In the present study, dose-response curves up to a total dose of 1000 mGy have been generated for photons from (125)I decay (approximately 30 keV) delivered at doses rates of 0.19, 0.47, 0.91 and 1.9 mGy/min. The results indicate that at dose rates of 1.9 and 0.91 mGy/min the slope of the induction curve is about 1.5 times less than that measured at high dose rate in previous studies with a similar quality of radiation (28 kVp mammographic energy X rays). In the dose region of 0 to 100 mGy, the data were equally well fitted by a threshold or linear no-threshold model. At dose rates of 0.19 and 0.47 mGy/min there was no induction of transformation even at doses up to 1000 mGy, and there was evidence for a possible suppressive effect. These results show that for this in vitro end point the DDREF is very dependent on dose rate and at very low doses and dose rates approaches infinity. The relative risks for the in vitro data compare well with those from epidemiological studies of breast cancer induction by low- and high-dose-rate radiation.

Cell Transformation, Neoplastic↗

PubMed2006

Predicting effects on aquatic organisms from fluctuating or pulsed exposure to pesticides.

Exposure of aquatic nontarget organisms to pesticides almost always occurs as pulses or fluctuating concentrations. Extrapolation from laboratory to field thus depends on an understanding and ability to simulate effects resulting from these types of exposure. This paper reviews models that may be used to predict effects on aquatic organisms resulting from time-varying exposure to pesticides. We evaluate and compare the theoretical basis of these models and their applicability to the simulation of effects from fluctuating exposures. The many different models rest on only a few basic concepts with differing degrees of mechanistic character. Building on this critical review, we select the most appropriate models and propose modifications. Two process-based models, the threshold hazard model and the modified damage assessment model, represent the optimum descriptions that are available at present. They could facilitate a better understanding of the ecotoxicity of different compound and species combinations and even mixtures of noninteracting compounds. The possibility to model lethal and sublethal effects allows applications in risk assessment, standard setting, and ecological modeling.

Animals↗

PubMed2002

A quantitative trait locus influencing type 2 diabetes susceptibility maps to a region on 5q in an extended French family.

Type 2 diabetes is a heterogeneous disorder of glucose metabolism characterized by insulin resistance, beta-cell dysfunction, and increased glucose production by the liver. Given the high degree of genetic heterogeneity, multiple genes with small to moderate effects may influence susceptibility to diabetes. To circumvent this limitation, we searched for quantitative trait loci (QTLs) that explain the variation in susceptibility of type 2 diabetes in a single extended family, as these individuals are likely to share polymorphisms. We collected genotypic and phenotypic data on 152 individuals ascertained through a multimedia campaign in France to find diabetes-prone families for genetic studies. The effects of genes and covariates (age and sex) on diabetes status were estimated using a threshold model and a maximum likelihood variance component approach. We obtained suggestive evidence of linkage (logarithm of odds [LOD] = 2.4) for diabetes status on chromosome 5q. Within the 1-LOD unit support interval, there are two strong candidates: PCSK1 and CAST. Furthermore, we have obtained a replication (LOD = 1.6) for a QTL for type 2 diabetes on chromosome 11 detected by Hanson and colleagues (1998).

Chromosome Mapping↗

PubMed2002

Evaluation of the genetic basis of tricuspid valve dysplasia in Labrador Retrievers.

OBJECTIVE: To quantify inheritance of tricuspid valve dysplasia (TVD) in a population of Labrador Retrievers and evaluate the possibility of the effect of a major locus on TVD. ANIMALS: 521 Labrador Retrievers (345 with known phenotypes and 176 related dogs with unknown phenotypes). PROCEDURES: Dogs were considered normal, equivocal, and affected for TVD on the basis of echocardiographic appearance of the tricuspid valves. Information on related dogs was collected for estimation of heritability of the 3 categories of phenotype, using a threshold model. Complex segregation analysis was performed to evaluate the possibility of the effect of a major locus on TVD. RESULTS: Heritability of TVD in this population of dogs was found to be 0.71, a value sufficiently large to suggest a segregating major locus. Subsequent complex segregation analysis did not provide sufficiently strong evidence to indicate influence of a major locus on the prevalence of TVD. However, complex segregation analysis for 2 categories of phenotype (eg, equivocal dogs were grouped with affected dogs) suggested that there was a single recessive allele with a substantial impact on the expression of TVD. CONCLUSIONS AND CLINICAL RELEVANCE: In Labrador Retrievers, TVD is a heritable disorder. Affected dogs and dogs closely related to affected dogs should not be used for breeding. There was insufficient evidence to suggest the influence of a major locus on TVD, although this conclusion was affected by the classification of dogs for diagnosis of the condition.

Alleles↗