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[Identification of major gene and polygene mixed inheritance model and estimation of genetic parameters of a quantitative trait from F2 progeny].

It has been proved by many field experiments and QTL mapping results that among genes affecting some quantitative traits there are some major genes with larger genetic effect and some polygenes with smaller genetic effect. For such traits, the distribution of segregating population demonstrates multimodality, and this is the characteristic of the mixture of more than one distributions. Mixture distribution models have been used extensively as models in a wide variety of practical situations where data can be viewed as arising from two or more populations mixed in certain proportions. Akaike's Information Criterion(AIC) has been used to identify the existence of major genes affecting quantitative traits. Under the existence of major genes, the genetic effects of these genes and their genetic variance were estimated through segregation analysis. The genotype of major gene of F2 individuals of were determined by clustering using Bayesian criterion. With P1, P2, F1 and F2 populations, the likelihood ratio test was used to test the existence of polygenes. In the end, the inheritance of soybean flowering date is analyzed. One major gene was found in F2 population derived from Guludou x Shanghaihongmangzao.

Models, Genetic↗

Multimodal map and complex basin of attraction of a simple hopper.

In this paper, we study the global dynamics of a simple passive mechanical model for hopping. The hopper is a two-mass, single-spring system constrained to move in the vertical direction (under gravity) above a rigid ground. The hopper model and its basic dynamics including the existence of incessant hopping motions have been reported elsewhere. Here, we extend the study to investigate the global dynamics of the hopper. The global map of the hopper is multimodal. We construct an approximate analytic map near the fixed points of the map and show that the fixed points exhibit one-way stability. We also show that the map is invariant under the inversion of the mass ratio of the hopper. Next, we construct the global basin of attraction of these fixed points and show that their structure is highly complex and retains form at finer scales. This structure of the basin of attraction contains regions where the fate of an arbitrary initial condition becomes unpredictable.

Journal Article↗

Automatic analysis of multimodal group actions in meetings.

This paper investigates the recognition of group actions in meetings. A framework is employed in which group actions result from the interactions of the individual participants. The group actions are modeled using different HMM-based approaches, where the observations are provided by a set of audiovisual features monitoring the actions of individuals. Experiments demonstrate the importance of taking interactions into account in modeling the group actions. It is also shown that the visual modality contains useful information, even for predominantly audio-based events, motivating a multimodal approach to meeting analysis.

Algorithms↗

Multimodal evaluation of therapy versus consultation components in a large inner-city early intervention program.

Cincinnati's Social Skills Development Program (SSDP) used a social competence model to direct its interventions for children. Systematic screening identified 15-25% of the primary grade children who showed behavioral problems and deficits in social skills at seven elementary schools. Multimodal evaluations comparing therapy and consultation interventions included three types of assessments over a 1 year period. Tests of social skills revealed that children who received both therapy and consultation services, compared to those who received only consultation, improved in a basic empathy skill and increased their externality in locus of control. School record data showed that therapy and consultation children improved in grades; but, consultation children improved most. Finally, trained observers found that therapy children, compared to children in consultation only, increased cooperative interactions with teachers and maintained appropriate solitary behaviors. The data are discussed as providing some support for the hypothesis that therapy produced increased benefits for children compared to the less costly consultation intervention. However, since therapy and consultation conditions were not differentiated on many assessments (e.g., tests of interpersonal problem-solving and advanced empathy skills; lateness; achievement), more intense behaviorally oriented interventions may be warranted.

Child↗

The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors.

PURPOSE: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. EXPERIMENTAL DESIGN: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+ suppressor cells. RESULTS: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non-self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). CONCLUSIONS: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.

Animals↗

An advanced boundary element method (BEM) implementation for the forward problem of electromagnetic source imaging.

The forward problem of electromagnetic source imaging has two components: a numerical model to solve the related integral equations and a model of the head geometry. This study is on the boundary element method (BEM) implementation for numerical solutions and realistic head modelling. The use of second-order (quadratic) isoparametric elements and the recursive integration technique increase the accuracy in the solutions. Two new formulations are developed for the calculation of the transfer matrices to obtain the potential and magnetic field patterns using realistic head models. The formulations incorporate the use of the isolated problem approach for increased accuracy in solutions. If a personal computer is used for computations, each transfer matrix is calculated in 2.2 h. After this pre-computation period, solutions for arbitrary source configurations can be obtained in milliseconds for a realistic head model. A hybrid algorithm that uses snakes, morphological operations, region growing and thresholding is used for segmentation. The scalp, skull, grey matter, white matter and eyes are segmented from the multimodal magnetic resonance images and meshes for the corresponding surfaces are created. A mesh generation algorithm is developed for modelling the intersecting tissue compartments, such as eyes. To obtain more accurate results quadratic elements are used in the realistic meshes. The resultant BEM implementation provides more accurate forward problem solutions and more efficient calculations. Thus it can be the firm basis of the future inverse problem solutions.

Algorithms↗

Pairwise comparisons of mitochondrial DNA sequences in subdivided populations and implications for early human evolution.

We consider the effect on the distribution of pairwise differences between mitochondrial DNA sequences of the incorporation into the underlying population genetics model of two particular effects that seem realistic for human populations. The first is that the population size was roughly constant before growing to its current level. The second is that the population is geographically subdivided rather than panmictic. In each case these features tend to encourage multimodal distributions of pairwise differences, in contrast to existing, unimodal datasets. We argue that population genetics models currently used to analyze such data may thus fail to reflect important features of human mitochondrial DNA evolution. These may include selection on the mitochondrial genome, more realistic mutation mechanisms, or special population or migration dynamics. Particularly in view of the variability inherent in the single available human mitochondrial genealogy, it is argued that until these effects are better understood, inferences from such data should be rather cautious.

Animals↗

[Recurrent abdominal pain].

BACKGROUND: Recurrent abdominal pain is found in 10-25% of school-aged children, thus being one of the most frequent complaints in childhood. Despite that, our knowledge about this syndrome is still very incomplete. DIAGNOSIS AND THERAPY: In the majority of cases, the traditional diagnostic approach understanding abdominal pain as a symptom of an underlying organic or psychological disease does not lead to a well-defined diagnosis with straightforward therapy. The natural course of abdominal pain in childhood seems to be less favorable than often assumed. Modern biopsychosocial models of recurrent abdominal pain are presented as a basis for future multimodal therapeutic concepts.

English Abstract↗

Analyzing a complex visuomotor tracking task with brain-electrical event related potentials.

Non-invasive techniques such as neuroimaging and event-related potential (ERP) methods have dramatically enhanced our understanding of the human brain. According to the requirements of the applied method, it is useful to simplify tasks for methodological reasons. In the present study we tested whether ERP measures are also suitable for analyzing complex tasks. In order to do this, we developed an analysis strategy based on the post hoc analysis of the behavioural data. We applied this method to a pursuit-tracking task of 25 s trial duration, consisting of repeated and non-repeated waveforms, where subjects had to track a target cross with a mouse-controlled cursor cross. An EEG was recorded from 62 channels. Response-locked ERPs were computed for two types of error correction: the correction of errors induced externally by the change of target direction and of internal errors generated by the subject itself. We found several ERP components that could be assigned to different feedback and feedforward controlled processing steps in the frontoparietal circuitry underlying visuomotor control, such as movement planning, movement execution (motor potential), reafferent activity, visuospatial analysis, and attentional (P300) processes. Our results support newer models that propose a role for the posterior parietal cortex in integrating multimodal sensory information. In addition, fast (about 180 ms and probably facilitated by anticipation) and slow (about 230-260 ms) error corrections could be differentiated by the time course of ERP activity. Our results show that complex (motor) tasks can be investigated with ERPs. This opens fruitful perspectives for future research on motor control in an ecological setting.

Adult↗

The meaning of a multimodal approach for children with ADHD: experiences of service professionals.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood mental disorder characterized by inattention, impulsiveness and overactivity. It is also characterized by heterogeneity and ambiguity. Effective intervention is influenced by these two factors. This pervasive disorder impacts various domains of functioning, including academics, peer relations, familial relationships and self-esteem. A confounding factor is the high rate of comorbidity with diagnoses such as learning disabilities, oppositional defiant disorder or conduct disorder. No one intervention has emerged as maximally effective across all symptoms and domains. Consequently, a multimodal approach is regarded as the favoured method of intervention. However, no clear definition of'multimodal' exists. METHOD: This study explored the meaning of multimodal from the perspective of professionals employed in a tertiary care hospital setting in which children with ADHD are assessed and treated. A qualitative design using a phenomenological approach allowed professionals to speak from their practice experiences. RESULTS AND CONCLUSION: Although no clear definition of multimodal emerged, professionals identified issues key to this approach and proposed a model for intervention.

Alberta↗

The need for standardized pathologic staging of pancreaticoduodenectomy specimens.

A standardized method for pathologic evaluation and staging of pancreaticoduodenectomy (PD) specimens is critical for accurate reporting of the number and location of lymph nodes and margins of resection. We examined the impact of standardized pathologic evaluation (SPE) of PD specimens on the identification of regional lymph nodes and describe our detailed system for the pathologic analysis of the PD specimen. Forty consecutive patients underwent PD for histologically confirmed adenocarcinoma of the pancreatic head between April 1990 and August 1993. Fifteen consecutive specimens were examined before the introduction of the SPE, and 25 consecutive specimens underwent SPE. Resection margins were evaluated by frozen-section analysis, and then the specimen was divided into six regions on an anatomic dissection board for lymph node identification. The 25 specimens examined according to the SPE had a significantly increased number of lymph nodes identified (P = 0.0001) compared with the 15 specimens examined without the SPE. Twelve of the 25 specimens contained positive lymph nodes, 6 of which were confined to the pancreaticoduodenal region. No positive nodes were found in the periaortic region. There were no differences in pathologic variables between patients found to have negative and those with positive regional lymph nodes. SPE of PD specimens provides a method for improved lymph node identification, ensures accurate prospective evaluation of margins of resection, and provides a complete analysis of potentially important pathologic variables. We offer this system as a standardized model for groups engaged in protocol-based clinical research examining innovative multimodality treatment strategies for patients with resectable pancreatic cancer.

Adenocarcinoma↗

Surface relaxation and chemical exchange in hydrating cement pastes: a two-dimensional NMR relaxation study.

We report the first nuclear magnetic resonance (NMR) two-dimensional correlation T(1) - T(2) and T(2) - T(2) measurements of hydrating cement pastes. A small but distinct cross peak in the two-dimensional relaxation spectrum provides the first direct evidence of chemical exchange of water between gel and capillary pores occurring over the first 14 days of hydration. A correlation of features along the line T(1) = 4T(2) provides strong supportive evidence for the surface diffusion model of (1)H nuclear spin relaxation in cements and for a multimodal discrete pore size distribution. Differences in detail of the results are reported for white cement paste and white cement paste with added silica fume. Both the method and the theory presented can be applied more widely to other high surface area materials with other reactive surface areas.

Journal Article↗

[Palliative treatment in gynecologic cancer].

BACKGROUND: Data on the need for palliative care related to disease groups are very limited. MATERIAL AND METHODS: A retrospective analysis was performed on the hospital records of 228 patients who died from gynaecologic cancer during the 1988-1997 period. RESULTS: 76% of deaths took place in hospital; 12% at home. Median terminal hospital stay was 13 days. Symptoms from intestinal obstruction were dominating in 30% of cases and most frequently seen in patients with ovarian cancer. Palliative intestinal surgery was performed in 38% of patients with ovarian cancer, median survival being 5 months (range 10 days-7 years), perioperative mortality (within 30 days) 13%. Cachexia dominated in 27% and was more often present when death occurred at home. Assistance from a gastroenterologic surgeon, urologist, haematologist or anaesthesiologist was needed in 32% of cases. One in two patients received parenteral pain relief in the terminal phase, for a median period of five days. Palliative radiotherapy was given 21% of the patients, most often in cervical and endometrial cancer, and chemotherapy or hormonal therapy was used in 36%. Minor interventions like laparocentesis, pleurocentesis, tumour resections, and various forms of urinary deviations were frequent. INTERPRETATION: Hospital deaths are more common among patients suffering from gynaecologic cancer than among cancer patients in general (55% in Norway), and the need for multimodal hospital service is large. We see substantial benefits in the Norwegian model in which a gynaecologist experienced in oncology has comprehensive responsibility for the treatment, supported by other specialists and the primary health service.

Adult↗

A comparative evaluation of multiple enlarged perivascular space segmentation tools.

BACKGROUND: Enlarged perivascular spaces (ePVS) are a marker of cerebral small vessel disease, potentially reflecting reduced waste clearance. Because manual quantification is unfeasible in large datasets, we developed and evaluated an automated tool. METHODS: Detection Of Regions of Enlarged perivascular Spaces (DORES), a 3D nnU-Net-based deep learning algorithm was developed for ePVS segmentation using T1-weighted and fluid-attenuated inversion recovery magnetic resonance imaging (MRI). DORES was developed in two stages: an initial model trained on 35 manually segmented scans and a final model on 1460 pseudo-labeled sessions from the Vanderbilt Memory and Aging Project (VMAP). A subset of VMAP participants with 3 T brain MRI underwent whole-brain manual ePVS tracing (n = 35, 73 ± 9 years, 51% male) and visual rating (n = 388, 71 ± 8 years, 54% male) by a neuroradiologist. DORES was evaluated and compared against three other segmentation tools using Dice and F1 scores, absolute volume and element differences, correlation, and agreement. External validation used an Alzheimer's Disease Neuroimaging Initiative 3 subset with manual tracings (ADNI3, n = 18, 73 ± 9 years, 67% female). RESULTS: DORES achieved Dice scores of 0.61 ± 0.16 (white matter) and 0.72 ± 0.08 (basal ganglia) in VMAP, with strong correlations and agreement for ePVS count and volume. Performances modestly declined in ADNI3 across algorithms. Scanner-stratified analyses showed stronger correlations for Philips versus Siemens images in the basal ganglia, indicating scanner-dependent differences in measurement consistency. CONCLUSIONS: DORES provides a multimodal nnU-Net-based pipeline for ePVS segmentation in older adults. The model demonstrates robust within-cohort performance and reasonable external validity, though scanner-related effects limit application across sites.

Humans↗

Bayesian modeling of dynamic scenes for object detection.

Accurate detection of moving objects is an important precursor to stable tracking or recognition. In this paper, we present an object detection scheme that has three innovations over existing approaches. First, the model of the intensities of image pixels as independent random variables is challenged and it is asserted that useful correlation exists in intensities of spatially proximal pixels. This correlation is exploited to sustain high levels of detection accuracy in the presence of dynamic backgrounds. By using a nonparametric density estimation method over a joint domain-range representation of image pixels, multimodal spatial uncertainties and complex dependencies between the domain (location) and range (color) are directly modeled. We propose a model of the background as a single probability density. Second, temporal persistence is proposed as a detection criterion. Unlike previous approaches to object detection which detect objects by building adaptive models of the background, the foreground is modeled to augment the detection of objects (without explicit tracking) since objects detected in the preceding frame contain substantial evidence for detection in the current frame. Finally, the background and foreground models are used competitively in a MAP-MRF decision framework, stressing spatial context as a condition of detecting interesting objects and the posterior function is maximized efficiently by finding the minimum cut of a capacitated graph. Experimental validation of the proposed method is performed and presented on a diverse set of dynamic scenes.

Algorithms↗

A multimodal, second generation, posttraumatic stress disorder rehabilitation program.

Second Generation posttraumatic stress disorder (PTSD) treatment programs were recently proposed as one component of a model of treatment of chronic PTSD. While First Generation PTSD programs emphasized trauma work, Second Generation programs emphasize skills for the present/future ability to adapt within society. The present paper describes a functioning Second Generation PTSD treatment program for Vietnam combat veterans. The guiding principles underlying this multimodal and vocational rehabilitation program are outlined.

Adaptation, Psychological↗

High-tech in radiation oncology: should there be a ceiling?

PURPOSE: To analyze some of the limitations to improvement of the outcome of radiotherapy (RT) expected from the introduction of sophisticated treatment planning and delivery technology. METHODS AND MATERIALS: Several recent examples from the literature were analyzed in some detail. Mathematical modeling techniques were used to assess the likely clinical impact of new technologies or biologic principles. The findings of recent randomized controlled trials of RT for prostate, breast, and rectal cancer were analyzed from the perspective of cost-effectiveness and therapeutic gain. RESULTS: The main findings of the analyses may be summarized as follows. Dosimetric precision should aim for a <2% patient-to-patient variability in the delivered dose. Imprecision in clinical target volume definition remains an obstacle for high-precision RT. Functional imaging and novel biologic assays may facilitate a move from a clinical target volume to the real target volume. Improved target volume coverage is mainly important if RT has high effectiveness. Radiation oncology is increasingly becoming evidence based. However, there is still a long way to go. Hypofractionation in adjuvant RT for breast cancer may represent a favorable balance between cost and benefit. Treatment complications are potentially associated with both suffering and high cost. The identification of high-risk patients would improve the cost-effectiveness of high-tech RT aimed at avoiding complications. Conformal RT may allow the introduction of hypofractionation, which, again, could potentially save resources. With improvement in surgery and more screening-detected cancer cases, the number needed to treat increases, and this will directly affect the cost-effectiveness of high-tech RT unless efficient patient selection can be developed. CONCLUSION: Sustained technological refinement is only likely to be cost-effective if the clinical and biologic understanding of patient-to-patient variability in the risk of specific types of failure and the optimal multimodality approach to handle these risks is developed at the same time. Mathematical modeling together with methods from health technology assessment and health economics are useful complements to standard methods from evidence-based medicine. Progress in functional imaging and in basic and clinical cancer biology is likely to provide the tools required for individualized risk-adapted RT.

Biological Assay↗