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PubMed2006

Methods to detect objects in photon-limited images.

We investigate the problem of detecting and localizing a known signal in a photon-limited image, where Poisson noise is the dominant source of image degradation. For this purpose we developed and evaluated three new algorithms. The first two are based on the impulse restoration (IR) principle and the third is based on the generalized likelihood ratio test (GLRT). In the IR approach, the problem is formulated as one of restoring a delta function at the location of the desired object. In the GLRT approach, which is a well-known variation on the optimal likelihood ratio test, the problem is formulated as a hypothesis testing problem, in which the unknown background intensity of the image and the intensity scale of the object are obtained by maximum-likelihood estimation. We used Monte Carlo simulations and localization receiver operating characteristic (LROC) curves to evaluate the proposed algorithms quantitatively. LROC curves demonstrate the ability of an algorithm to detect and locate objects in a scene correctly. Our simulations demonstrate that the GLRT approach is superior to all other tested algorithms.

Algorithms↗
PubMed1978

Letter identification as a function of type of perceptual limitation and type of attribute.

It is argued that the distribution of errors in letter identification depends on two factors: (a) whether the set of letters is defined by features that exist or do not exist or by dimensions that exist at some positive value, and (b) whether errors are produced by process limitation in which the letter patterns are distorted or by state limitation in which there is inadequate energy. A specific hypothesis tested was that error distributions reflect the attribute structure under both types of limitation if dimensions define the letter set, but only under a process limitation if features define the letter set. Under a state limitation, feature set errors are primarily produced by a loss of features, so that a letter with more features is called a letter with fewer features more often than conversely. An experiment completely validated the hypothesis under test. In addition, the relative discriminabilities of two dimensions defining a dimension set of letters was reversed from state to process limitation. Thus the attribute structure derived from error distributions is not invariant across types of perceptual limitation, nor are distances between letter pairs always symmetric.

Discrimination, Psychological↗
PubMedDate not supplied

Protective effect of HMG-CoA reductase inhibitor on experimental renal ischemia-reperfusion injury.

BACKGROUND: Increasing evidence supports an important role for inflammation in the pathogenesis of renal ischemia-reperfusion injury (IRI). Recently, HMG-CoA reductase inhibitors, 'statins', have demonstrated anti-inflammatory effects independent of cholesterol-lowering. HYPOTHESIS: We tested the hypothesis that a statin would improve outcome in a murine model of renal IRI. Upon finding a protective effect, we tested the hypothesis that the mechanisms by which statins protected in renal IRI was by reducing neutrophil and macrophage infiltration and upregulating the anti-inflammatory cytokine IL-6. METHODS: Cerivastatin at various dosing regimens was administered to NIH Swiss mice to evaluate the effects on renal IRI. Analysis of renal structure, function, neutrophil and macrophage infiltration, cytokine production, as well as mortality was performed in cerivastatin- and saline-treated groups. RESULTS: PRIMARY: Cerivastatin pretreatment for 3 days led to a significant improvement in renal function, tubular injury as well as survival after IRI compared to saline-treated mice. SECONDARY: Neutrophil and macrophage infiltration into kidney tissue was similar in both groups. IL-6 was markedly upregulated early in the kidneys of statin-treated compared to saline-treated mice. CONCLUSION: These data demonstrate that a statin compound can improve the course of ischemic acute renal failure. Induction of protective molecules such as IL-6 may underlie this effect.

Animals↗
PubMed1983

Clinical inferences and decisions--I. Diagnosis and Bayes' theorem.

Clinical decisions are based upon inferences derived from test evidence where data is collected as a means of hypothesis testing. In medicine, the initial expectation of a clinical state is rarely expressed in the classical scientific language of a null hypothesis where alternative outcomes are assumed to be equally probable, because clinical experience reinforces the maxim that common events occur commonly. The collection of test evidence in clinical practice, therefore, is directed towards overturning prior likelihoods for a clinically pathological state which are far from mere chance expectations. The extent to which any test evidence can modify such prior expectations not only depends on its relevance to the clinical state in question (i.e. the hypothesis) but also is largely influenced by the inherent error rates in the test itself. Clinical decision models should reflect these facts. Using examples from the field of ophthalmology, this paper presents a normative model using Bayes' theorem of conditional probabilities which provides a rational framework upon which to base or appraise clinical decisions. Parts II and III of the series will expand this clinical application of decision theory to show how it may be used in the absence of hard test evidence and also where a different emphasis or utility may be placed on false positive or false negative errors.

Bayes Theorem↗
PubMed2000

Family-based tests of association in the presence of linkage.

Linkage analysis may not provide the necessary resolution for identification of the genes underlying phenotypic variation. This is especially true for gene-mapping studies that focus on complex diseases that do not exhibit Mendelian inheritance patterns. One positional genomic strategy involves application of association methodology to areas of identified linkage. Detection of association in the presence of linkage localizes the gene(s) of interest to more-refined regions in the genome than is possible through linkage analysis alone. This strategy introduces a statistical complexity when family-based association tests are used: the marker genotypes among siblings are correlated in linked regions. Ignoring this correlation will compromise the size of the statistical hypothesis test, thus clouding the interpretation of test results. We present a method for computing the expectation of a wide range of association test statistics under the null hypothesis that there is linkage but no association. To standardize the test statistic, an empirical variance-covariance estimator that is robust to the sibling marker-genotype correlation is used. This method is widely applicable: any type of phenotypic measure or family configuration can be used. For example, we analyze a deletion in the A2M gene at the 5' splice site of "exon II" of the bait region in Alzheimer disease (AD) discordant sibships. Since the A2M gene lies in a chromosomal region (chromosome 12p) that consistently has been linked to AD, association tests should be conducted under the null hypothesis that there is linkage but no association.

Algorithms↗
PubMed1989

Pharmacotherapy for self-injurious behavior: preliminary tests of the D1 hypothesis.

The D1 dopamine hypersensitivity model of self-injurious behavior leads to a testable clinical hypothesis: the mixed D1/D2 dopamine antagonist fluphenazine may improve the symptoms of self-injurious patients. The hypothesis was tested in an open pilot trial in six patients and a partially controlled trial in nine patients. Some degree of clinical improvement was observed in 11 of the 15 patients. The trials represent a partial affirmation of the D1 hypothesis. However, it is also clear that conventional methodology for psychopharmacologic research is inappropriate for the proper clinical evaluation of self-injurious patients. The proper method should include the following elements: 1. An epidemiologically representative sample. 2. A naturalistic study environment. 3. A longitudinal design with long-term follow up. 4. Concurrent behavioral ratings using direct observations and a reliable, treatment-sensitive rating scale. Before subjects enter a clinical trial of an experimental medication, a neuropsychiatric differential diagnosis should be applied to limit the diversity of the sample.

Adult↗
PubMed2003

Behavioral characterization of 2-O-desmethyl and 5-O-desmethyl metabolites of the phenylethylamine hallucinogen DOM.

The present investigation was undertaken to test the hypothesis that known metabolites of the phenylethylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) are pharmacologically active. This hypothesis was tested by evaluating the ability of racemic DOM metabolites 2-O-desmethyl DOM (2-DM-DOM) and 5-O-desmethyl DOM (5-DM-DOM) to substitute for the stimulus properties of (+)lysergic acid diethylamide (LSD). The data indicate that both metabolites are active in LSD-trained subjects and are significantly inhibited by the selective 5-HT(2A) receptor antagonist M100907. Full generalization of LSD to both 2-DM-DOM and 5-DM-DOM occurred, and 5-DM-DOM was slightly more potent than 2-DM-DOM. Similarly, 5-DM-DOM had a slightly higher affinity than 2-DM-DOM for both 5-HT(2A) and 5-HT(2C) receptors. Additionally, it was of interest to determine if the formation of active metabolite(s) resulted in a temporal delay associated with maximal stimulus effects of DOM. We postulated that if metabolite formation resulted in the aforementioned delay, direct administration of the metabolites might result in maximally stable stimulus effects at an earlier pretreatment time. This hypothesis was tested by evaluating (1) the time point at which DOM produces the greatest degree of LSD-appropriate responding, (2) the involvement of 5-HT(2A) receptor in the stimulus effects of DOM at various pretreatment times by administration of M100907 and (3) the ability of 2-DM-DOM and 5-DM-DOM to substitute for the stimulus properties of LSD using either 15- or 75-min pretreatment time. The data indicate that (a) the DOM stimulus produces the greatest degree of LSD-appropriate responding at the 75-min time point in comparison with earlier pretreatment times and (b) the stimulus effects of DOM are differentially antagonized by M100907 and this effect is a function of DOM pretreatment time prior to testing. Both 2-DM-DOM and 5-DM-DOM were found to be most active, at all doses tested, using a 75-min versus a 15-min pretreatment time. The present data do not permit unequivocal acceptance or rejection of the hypothesis that active metabolites of (-)-DOM provide a full explanation of the observed discrepancy between brain levels of (-)-DOM and maximal stimulus effects.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1990

Pharmacotherapy for self-injurious behavior: preliminary tests of the D1 hypothesis.

1. The D1 dopamine hypersensitivity model of self-injurious behavior leads to a testable clinical hypothesis: that the mixed D1/D2 dopamine antagonist fluphenazine may improve the symptoms of self-injurious patients. 2. The hypothesis was tested in an open pilot trial in six patients and a partially controlled trial in nine patients. 3. Some degree of clinical improvement was observed in eleven of the fifteen. 4. The trials represent a partial affirmation of the D1 hypothesis. However, it is also clear that conventional methodology for psychopharmacologic research is inappropriate for the proper clinical evaluation of self-injurious patients. The proper method should include the following elements: i) An epidemiologically representative sample ii) A naturalistic study environment iii) A longitudinal design with long-term follow-up iv) Concurrent behavioral ratings using direct observations and a reliable, treatment-sensitive rating scale. 5. Before subjects enter a clinical trial of an experimental medication, a neuropsychiatric differential diagnosis should be applied to limit the diversity of the sample.

Adolescent↗
PubMed2002

The parasite-induced surfacing behaviour in the cockle Austrovenus stutchburyi: a test of an alternative hypothesis and identification of potential mechanisms.

The New Zealand cockle Austrovenus stutchburyi, whose foot is commonly infected by the digenean trematode Curtuteria australis (Echinostomatidae), is often found heavily infected and unable to burrow on the sediment surface of tidal flats. This has been interpreted as a Curtuteria-manipulation with the purpose of increasing the transmission of the parasite to shorebirds acting as final hosts. Using a field-experimental approach the alternative hypothesis was tested, that surface-dwelling cockles, caught on the surface for other reasons than parasites, accumulate larval C. australis at a higher rate than buried cockles. During the 3-month experiment, larval trematodes accumulated with a rate of approximately 0.5 metacercariae/day in both surface and buried cockles. The result strengthens the manipulation hypothesis indirectly by rejecting the alternative hypothesis. The metacercariae were unevenly distributed along the cockle-foot, with about 4 times as many cysts being found in the tip than in either the mid or hind part of the foot. In light of existing knowledge of the burrowing behaviour and apparatus in bivalves, and a negative relationship between foot mobility and infection intensity, it is suggested that C. australis manipulates its host through a mechanical obstruction of foot muscles and the dynamic hydrostatic skeleton, both necessary for successful burrowing.

Adaptation, Physiological↗
PubMed1995

Gender and the use of neuroleptics in schizophrenia. Further testing of the oestrogen hypothesis.

According to the oestrogen hypothesis, the lower need for neuroleptic drugs in female schizophrenics is caused by the antidopaminergic effect of oestrogens. Due to the decreased oestrogen production during the menopause, this 'neuroleptic' effect is lost and the need for neuroleptic drugs increases in female schizophrenics. This hypothesis was tested by studying a sample of 1097 schizophrenic patients (DSM-III-R), who were discharged from hospital and followed for three years. Prescribed daily doses of neuroleptic drugs were recorded and converted to chlorpromazine equivalents. Males had higher daily doses of neuroleptics than females; this gender difference, however, was only significant in middle-aged groups. Daily doses were also associated with age at the onset of illness, duration of illness and clinical status. Results did not support the oestrogen hypothesis: In females, there was no consistent increase in daily doses of neuroleptics after menopause age. Results are discussed from the viewpoint of testosterone secretion, body weight and smoking habits, which are gender-bound and thus can, at least in part, explain gender differences in the use of neuroleptic drugs in schizophrenic patients. It is pointed out that the age at the onset of illness and the duration of illness should be taken into account when the effects of gender and age on the need for neuroleptics are studied.

Adolescent↗
PubMed2006

Chronic pain: a non-use disease.

One of the major problems in modern medicine is to find remedies for the group of people with chronic pain syndromes. Low back pain is one of the most frequent syndromes and perhaps the most invalidating of all of them. Chronic pain seems to develop through several pathways affecting the spinal cord and the brain: (1) neuro-anatomical reorganisation, (2) neuro-physiological changes, and (3) activation of glia cells (immune reaction in the central nervous system). Although all of these pathways seem to provide a (partial) plausible explanation for chronic pain, treatments influencing these pathways often fail to alleviate chronic pain patients. This could be because of the probability that chronic pain develops by all three mechanisms of disease. A treatment influencing just one of these mechanisms can only be partially successful. Other factors that seem to contribute to the development of chronic pain are psychosocial. Fear, attention and anxiety are part of the chronic pain syndrome being cause or consequence. The three pathways and the psycho-emotional factors constitute a psycho-neuro-immunological substrate for chronic pain syndromes; a substrate which resembles the substrate for phantom pain and functional invalidity after stroke. Both phantom pain and functional invalidity are considered non-use syndromes. The similarity of the substrate of both these two neurological disorders and chronic pain makes it reasonable to consider chronic pain a non-use disease (the hypothesis). To test this hypothesis, we developed a "paradoxal pain therapy". A therapy which combines the constraint induced movement therapy and strategies to dissociate pain from conditioning factors like fear, anxiety and attention. The aim of the therapy is to establish a behaviour perpendicular on the pathological pain-behaviour. Clinically, the treatment seems promising, although we just have preliminary results. Further clinical and laboratory studies are needed to measure eventual changes at neuro-anatomical and neuro-psychological level using modern neuro-imaging instruments (PET, SPECT, fMRI). Randomised clinical trials should be carried out to test our hypothesis for all-day use in clinical practice. The hypothesis: chronic pain is a non-use disease produced by psycho-emotional factors like fear, attention and anxiety. Optimal treatment should be based on physiological use, and dissociation of pain and the mentioned psycho-emotional factors. Paradoxal pain therapy could serve these treatment conditions.

Chronic Disease↗
PubMed1990

Changes in reproductive function among remarried women: the effects of spousal characteristics.

"This paper examines the relationship between change in childbearing function from a woman's first to second marriage and the degree of similarity between her first and second husbands in age, education, and religion. Using data from the [U.S.] 1982 National Survey of Family Growth, the specific hypothesis tested is: where plans are similar, the second husband tends to resemble the first to a greater extent than where childbearing functions differ. Separate tests relating to age, education, and religion provide only limited support for this hypothesis. However, when the various tests are considered collectively as a system, the weight of the evidence provides general support for the hypotheses. The implications of these findings for understanding trends in marriage are discussed."

Americas↗
PubMed2005

Variation in femoral length is associated with polymorphisms in RUNX2 gene.

INTRODUCTION: Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested. MATERIALS AND METHODS: The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis. RESULTS: The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females (P = 0.007) than in males (P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found. CONCLUSIONS: For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.

Adolescent↗
PubMed2001

Dephosphorylation of sodium caseinate, enzymatically hydrolyzed casein and casein phosphopeptides by intestinal alkaline phosphatase: implications for iron availability.

Clusters of phosphoserine residues in casein bind iron with high affinity. Casein inhibits iron absorption in humans but partial hydrolysis of casein prior to ingestion diminishes this inhibition. The objective of this study was to test two hypotheses: 1. Partial hydrolysis of the peptide bonds in casein exposes phosphoserine residues to attack by intestinal alkaline phosphatase (IAP). 2. Hydrolysis of the phospho-ester linkage in phosphoserine residues in casein by IAP releases bound iron or inhibits iron chelation, thereby allowing its absorption. Test of hypothesis 1: Suspensions of sodium caseinate (SC), enzymatically hydrolyzed casein (EHC), and casein phosphopeptides (CPP) were subjected to an in vitro pepsin/pancreatin digestion and subsequently incubated in the presence of calf IAP. The rate of release of inorganic phosphate was measured with the following results (expressed as &mgr;mol phosphate released/unit of IAP/min): 0.081, 0.104, 0.139 for SC, EHC, and CPP, respectively. These results are consistent with hypothesis 1. Test of hypothesis 2: (59)Fe-citrate or (59)Fe-citrate + CPP in minimum essential media were spiked with a Na(2)WO(4) solution or water (Na(2)WO(4) is a known inhibitor of IAP) and placed on Caco-2 cell monolayers. Uptake of (59)Fe by the cells was used as an index of iron bioavailability. Na(2)WO(4) did not affect (59)Fe uptake from samples containing only iron but did slightly inhibit (by 10%) uptake from samples containing iron + CPP. These results are consistent with hypothesis 2 and provide a possible explanation for the observation that partial hydrolysis of casein improves iron bioavailability.

Journal Article↗
PubMed1991

Apparent size as a function of vertical gaze direction: new tests of an old hypothesis.

The hypothesis was tested that the decline of apparent size with elevated gaze results from a latent tendency of the eyes to diverge and thus increased vergence effort. Through the use of a method of category estimation, the decline of apparent size on elevation or depression of gaze was found not to be different between subjects with larger or smaller changes of dark vergence and thus vergence effort. In a 2nd experiment, vergence effort was varied by varying gaze elevation and the angle of convergence. With vergence effort constant, apparent size was dependent on the angle of convergence rather than being constant. It is concluded that apparent size does not depend on vergence effort and that the effect of gaze elevation on apparent size cannot be attributed to its concomitant effect on dark vergence.

Adolescent↗
PubMed1995

Issues in biomedical statistics: comparing means by computer-intensive tests.

In this review there are described two alternatives to classical tests for distinguishing means. These are called computer-intensive because they can only be performed on fast computers. Permutation procedures have the virtue in that they are easy to understand, they can be employed to analyse small sets of experimental data, and under the randomization model of inference (though not the population model) they require no assumptions except that the experimental groups have been constructed by randomization. Bootstrap procedures are designed for use under the population model of inference (though not the randomization model) and are best suited to larger sets of experimental data. Non-parametric bootstrapping requires populations to be sampled randomly, but it depends on no prior assumptions about the distributions of those populations. It is argued that if randomization rather than random sampling has been done, permutation tests are superior to the classical t and F tests for detecting differences between means and therefore should replace them. If random sampling has been done, non-parametric bootstrap techniques may prove to be superior to classical tests for constructing population confidence intervals or testing hypotheses. However, their accuracy, especially for hypothesis-testing and when samples are small, has yet to be firmly established and there is a dearth of commercial software with which they can be executed on personal computers.

Computer Simulation↗
PubMed1991

Capillary spatial pattern and muscle fiber geometry in three hamster striated muscles.

Since most oxygen exchange in muscle is thought to occur by diffusion across the walls of capillaries, it is important to determine the spatial relationship between capillaries and muscle fibers. We have extended the work of Kayar et al. (Microvasc. Res 24: 326-341, 1982) to include other statistical tests that allow one to make stronger statements regarding the spatial pattern. Data for hamsters were obtained from two sartorius, three retractor, and five soleus muscle sections. Distances between all pairs of capillaries, distances between a capillary and its first nearest neighbor for all capillaries, and distances between random tissue sample points and the closest capillary were used to test the spatial arrangement of capillaries. The null hypothesis tested of complete spatial randomness of capillary locations was rejected in favor of a regular alternative in one each of the sartorius and retractor fields and in all five soleus fields. We formulated a geometric model, composed of a space-filling array of identical hexagonal muscle fibers with capillaries placed randomly at the juncture of three fibers or between two fibers, according to the observed relative probability of those occurrences. The model simulations of muscle fibers and capillaries were then analyzed by the same statistical tests used on the histological sections. The findings were similar in both cases, providing confidence that the assumptions of the model were sufficient approximations. The results of this study provide a basis for the placement of capillaries around muscle fibers in mathematical models of oxygen transport in capillary networks.

Animals↗
PubMed1984

Personality tests as a predictor of success in a residential treatment center.

This study compares the profiles of two groups of emotionally disturbed female adolescents as measured by two objective personality tests, the HSPQ and the Jesness Inventory. The hypothesis tested was that the unsuccessful girls would score significantly differently on various dimensions of the two tests than the successful girls. Unsuccessful girls were those who did not complete the treatment program; successful girls were those who completed the program. A comparison of the mean scores of the various personality factors on each test showed significant differences upon admission.

Acting Out↗