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PubMed2000

The episodic buffer: a new component of working memory?

In 1974, Baddeley and Hitch proposed a three-component model of working memory. Over the years, this has been successful in giving an integrated account not only of data from normal adults, but also neuropsychological, developmental and neuroimaging data. There are, however, a number of phenomena that are not readily captured by the original model. These are outlined here and a fourth component to the model, the episodic buffer, is proposed. It comprises a limited capacity system that provides temporary storage of information held in a multimodal code, which is capable of binding information from the subsidiary systems, and from long-term memory, into a unitary episodic representation. Conscious awareness is assumed to be the principal mode of retrieval from the buffer. The revised model differs from the old principally in focussing attention on the processes of integrating information, rather than on the isolation of the subsystems. In doing so, it provides a better basis for tackling the more complex aspects of executive control in working memory.

Journal Article↗
PubMed1990

Right and left orientation in children aged 5 to 13 years.

A 32-item test of right/left orientation was administered to 360 normal children, aged 5 to 13 years. The distribution of scores was tested to determine if parametric descriptive statistics were appropriate. As the distribution was multimodal, the test of normality was rejected. The three modes were consistent with a stage development theory, with the respective modes being consistent with (a) no understanding of right/left, (b) a personal or egocentric understanding of right/left, and (c) a generalization of right/left to external objects. Therefore, the data are presented in terms of the probability of obtaining a specific score at a given age. Scores were not found to be related to sex and were weakly, if at all, related to level of psychometric intelligence.

Adolescent↗
PubMed2002

Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition.

Progression to renal parenchymal damage and end-stage renal disease, which seems to be largely independent of the initial insult, is the final common pathway for chronic, proteinuric nephropathies in animals and humans. The key event is enhanced glomerular capillary pressure; this impairs glomerular permeability to proteins and permits excessive amounts of proteins to reach the lumen of the proximal tubule. The secondary process of reabsorption of filtered proteins can contribute to renal interstitial injury by activating intracellular events, including upregulation of the genes encoding vasoactive and inflammatory mediators. Both interstitial inflammation and progression of disease can be controlled by such drugs as angiotensin-converting enzyme inhibitors, which strengthen the glomerular permeability barrier to proteins and thereby limit proteinuria and filtered protein-dependent inflammatory signals. Clinical data strongly suggest that remission can now be achieved in some patients with chronic renal disease. Because of the current lag time between starting treatment and remission, however, a substantial proportion of patients still progress to end-stage renal disease before renal function begins to stabilize. A multimodal approach that centers on reducing or removing all risk factors associated with the progression of renal disease may decrease the time to remission of the disease for most patients with proteinuric nephropathies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[Results of surgical therapy of choledocholithiasis--a retrospective study].

A multimodal therapeutic concept of choledocholithiasis with endoscopic and surgical procedures is presented. Between January 1986 and December 1990 106 patients with choledocholithiasis were operated. These patients are retrospectively analyzed. The success rate is 95.3%, the morbidity 18.7% and the mortality 0. These results are compared with the published data of the surgical or endoscopic therapy of the choledocholithiasis.

Adolescent↗
PubMed1995

Efficacy of multimodality spinal cord monitoring during surgery for neuromuscular scoliosis.

STUDY DESIGN: This study determined the relative efficacy of somatosensory-evoked potentials and motor-evoked potentials in monitoring spinal cord function during surgery for patients with idiopathic versus neuromuscular scoliosis. OBJECTIVES: To determine whether patients with idiopathic versus neuromuscular scoliosis demonstrate significantly different somatosensory-evoked potentials and motor-evoked potentials recorded during surgery. SUMMARY OF BACKGROUND DATA: Ashkenaze et al (1993) and others have reported that cortical somatosensory-evoked potentials are unreliable when used to monitor spinal cord function in patients with neuromuscular scoliosis. It was recommended that other neurophysiologic tests be used. METHODS: Somatosensory-evoked potentials and motor-evoked potentials were recorded from two groups of patients: those with idiopathic scoliosis and those with neuromuscular scoliosis. Somatosensory-evoked potentials were obtained before and during surgery. Motor-evoked potentials were obtained during surgery. Normal variability, as indicated from idiopathic scoliotic results, was compared with data obtained from patients with neuromuscular scoliosis. Motor-evoked potentials and somatosensory-evoked potentials were obtained sequentially during the duration of surgery. RESULTS: Single-channel cortical somatosensory-evoked potentials demonstrated a 27% positive rate, which was consistent with results (28%) from Ashkenaze et al. The use of multiple recording sites for the somatosensory-evoked potentials and the addition of motor-evoked potential procedures indicated that a reliable response could be obtained in more than 96% of the patients. It also was found that cortical somatosensory-evoked potentials were more affected by anesthetic agents when recorded from patients with neuromuscular scoliosis compared with patients with idiopathic scoliosis. CONCLUSIONS: Single-channel cortical somatosensory-evoked potentials demonstrated a high level of unreliability, which reduced their clinical effectiveness. However, by using multiple recording sites with the somatosensory-evoked potentials and by administering motor-evoked potential procedures, it was possible to monitor spinal cord function in neuromuscular patients and avoid postoperative neurologic deficits.

Adolescent↗
PubMed1984

Surgical oncology.

There has been a recent reassertion of the surgeon's role in cancer management. Traditionally, surgery has been the major modality of cancer treatment. In settings of clinical trials, surgeons had initially assumed a more passive status, contributing patients while chemotherapists and radiotherapists developed experimental protocols. Currently surgeons are taking an active role in planning and participating in such clinical studies. The American Joint Committee Staging System is being widely adopted, quality control of surgical procedures is improving, and innovative surgical operations are being devised. Surgical oncologists have spearheaded the concepts of multimodal treatment for their colleagues for a variety of cancers, most particularly cancers of the breast, head and neck, esophagus, lung, stomach, colorectum, and testicles, and sarcomas. The interaction of surgical treatment with radiation and chemotherapy is now more carefully planned, both for primary and metastatic tumors, and meaningful data are being derived from patient care. There is emphasis on treatment options, individualization of therapy, and restorative procedures at a variety of cancer sites. Constitutional aspects of cancer, such as nutrition, immune status, and metabolic aberrations, are given more attention, and there is a greater application of advances in cancer biology to the overall clinical care of patients.

Clinical Trials as Topic↗
PubMed1985

Localized Ewing's sarcoma of bone: ten years' experience at the Istituto Ortopedico Rizzoli in 124 cases treated with multimodal therapy.

The results obtained in the treatment by multimodal therapy (surgery, radiation therapy and chemotherapy) of 124 cases of Ewing's sarcoma are presented. At a medium follow-up of 65 months 48% of the patients are disease-free. One patient died of leukemia and two patients developed an irradiation-induced sarcoma. Analysing the data, three factors seem to be correlated to prognosis: location of the initial lesion outside the pelvis and sacrum, a four-drug chemotherapy protocol and the use of surgery in the treatment of the initial lesion seem to give better results.

Adolescent↗
PubMed2025

Nonlinear transcriptional responses to gradual modulation of transcription factor dosage.

Genomic loci associated with common traits and diseases are typically non-coding and likely impact gene expression, sometimes coinciding with rare loss-of-function variants in the target gene. However, our understanding of how gradual changes in gene dosage affect molecular, cellular, and organismal traits is currently limited. To address this gap, we induced gradual changes in gene expression of four genes using CRISPR activation and inactivation. Downstream transcriptional consequences of dosage modulation of three master trans-regulators associated with blood cell traits (GFI1B, NFE2, and MYB) were examined using targeted single-cell multimodal sequencing. We showed that guide tiling around the TSS is the most effective way to modulate cis gene expression across a wide range of fold-changes, with further effects from chromatin accessibility and histone marks that differ between the inhibition and activation systems. Our single-cell data allowed us to precisely detect subtle to large gene expression changes in dozens of trans genes, revealing that many responses to dosage changes of these three TFs are nonlinear, including non-monotonic behaviours, even when constraining the fold-changes of the master regulators to a copy number gain or loss. We found that the dosage properties are linked to gene constraint and that some of these nonlinear responses are enriched for disease and GWAS genes. Overall, our study provides a straightforward and scalable method to precisely modulate gene expression and gain insights into its downstream consequences at high resolution.

Journal Article↗
PubMed1983

The diagnosis and classification of multiple sclerosis: evoked responses and spinal fluid electrophoresis.

Multimodality evoked responses (including visual, brainstem auditory, and somatosensory) and CSF analysis were evaluated in 123 patients grouped into definite, probable, and possible MS according to the McAlpine criteria. The evoked responses (ERs) were very sensitive in detecting asymptomatic lesions and can therefore be used in conjunction with clinical data to provide evidence of multiple lesions. The CSF abnormalities also have high sensitivity and specificity in MS. ER and CSF findings, therefore, should be considered in addition to the clinical data in any classification of MS.

Adolescent↗
PubMed1995

Cluster analysis of levels of body fatness in children.

The purpose of this study was to examine, using cluster analysis, the levels of body fatness as defined in the current national programs for children and youth fitness. A total of 1,056 examinees were drawn randomly from the published data of the National Children and Youth Fitness Study II, with 525 boys and 531 girls, ages 6 to 9 years. Their triceps and medial calf skinfold measures were used for the cluster analysis, including both the kth nearest-neighbor and the Ward's minimum variance procedures. Although multimodal clusters were found at four age groups according to the kth nearest-neighbor procedure, the Ward procedure and plotting of these clusters did not support their existence. It was concluded that the levels of body fatness reported in the current national children and youth fitness programs were arbitrarily defined.

Child↗
PubMed1988

Standardization and analysis of digitized photographic data in the longitudinal documentation of cataractous growth.

Age-related cataract formation in man can be documented with slit and retroillumination photographs. With digitization and image analysis of such photographs a cataract may be characterized by a frequency distribution of picture elements over a 255 step gray scale spectrum. Transition from a clear to a cataractous lens may be manifested as a change from a unimodal, Gaussian to a multimodal, non Gaussian frequency distribution respectively. How should one compare and contrast these two distributions, so to accurately describe the extent and significance of a change in lens opacification? The in vitro system of cold cataract formation in the rabbit lens was used as a model of the much slower process of age-related cataract formation in man. As in the human lens undergoing progressive opacification, the frequency distribution (number of pixels vs. intensity of gray) for a digitized image of a clear lens at 26 degrees C is unimodal and Gaussian; that of a fully developed cold cataract at 10 degrees C is multimodal and non-gaussian. In spite of the increasing multimodality of the frequency distribution as the temperature dropped and the cataract grew in density and size, the mean gray density proved to be a valid and useful measure to characterize the distribution and to compare different unaligned images. The Wilcoxon Rank Sum Test proved to be useless in comparing the frequency distributions from cataract images because it proved to be too sensitive to subtle changes in the degree of opacification. Anomalous behavior of the opacification process--i.e. clarification as well as opacification of the lens during cold cataract formation caused all pairs to appear statistically significantly different when in appearance there was no difference. The mean of the frequency distribution is less sensitive to this anomalous behavior and is useful as a comparative index. The method of calculating the threshold of significant change in the mean density of a cataract image is presented.

Animals↗
PubMed2003

Multimodal image fusion in ultrasound-based neuronavigation: improving overview and interpretation by integrating preoperative MRI with intraoperative 3D ultrasound.

OBJECTIVE: We have investigated alternative ways to integrate intraoperative 3D ultrasound images and preoperative MR images in the same 3D scene for visualizing brain shift and improving overview and interpretation in ultrasound-based neuronavigation. MATERIALS AND METHODS: A Multi-Modal Volume Visualizer (MMVV) was developed that can read data exported from the SonoWand neuronavigation system and reconstruct the spatial relationship between the volumes available at any given time during an operation, thus enabling the exploration of new ways to fuse pre- and intraoperative data for planning, guidance and therapy control. In addition, the mismatch between MRI volumes registered to the patient and intraoperative ultrasound acquired from the dura was qualified. RESULTS: The results show that image fusion of intraoperative ultrasound images in combination with preoperative MRI will make perception of available information easier by providing updated (real-time) image information and an extended overview of the operating field during surgery. This approach will assess the degree of anatomical changes during surgery and give the surgeon an understanding of how identical structures are imaged using the different imaging modalities. The present study showed that in 50% of the cases there were indications of brain shift even before the surgical procedure had started. CONCLUSIONS: We believe that image fusion between intraoperative 3D ultrasound and preoperative MRI might improve the quality of the surgical procedure and hence also improve the patient outcome.

Brain↗
PubMed2000

Neurophysiologic exploration: a reliable tool in HIV-1 encephalopathy diagnosis in children.

BACKGROUND: HIV-1 related encephalopathy has a bad prognostic meaning in the course of AIDS disease, but the early association of different drugs can modify its course. For this reason it is very important to recognize CNS involvement as soon as possible. As shown in the literature, at least in adult studies, EEG and Evoked Potentials (EP) are good tools in evaluating CNS alterations. In children data are rare. METHODS: A ten-year prospective study of 44 infected children out of 142 born from HIV-1 positive mothers has been done. The children have been submitted to EEG recording every six months in the first 18 months of life and then every year, to multimodal EP every six months. A total of 357 EEG, 47 P-VEP, 62 F-VEP and 98 BAEP have been performed. RESULTS: EEG: we found no pathologic results in patients belonging to category A; results were pathologic in 17.7% in category B, in 47.7% in C and in 77% of encephalopathic patients. It seems that EEG alterations are parallel to disease progression, with a relative risk of developing encephalopathy (R.R. = 1.15) and of death (R.R. = 2.33) for patients belonging to category C. We obtained a statistically significant lengthening in BAEP interpeak latency of left ear in all groups. For patients in category C the risk of developing encephalopathy is statistically significant (p = 0.045; R.R. = 6.75) and risk of death is high (R.R. = 4). CONCLUSIONS: Neurophysiologic exams are a reliable tool for the diagnosis of encephalopathy, in addition to clinical evidence.

AIDS Dementia Complex↗
PubMed2003

Slot: a research platform for investigating multimodal communication.

In this article, we present the spatial logistics task (SLOT) platform for investigating multimodal communication between 2 human participants Presented are the SLOT communication task and the software and hardware that has been developed to run SLOT experiments and record the participants' multimodal behavior. SLOT offers a high level of flexibility in varying the context of the communication and is particularly useful in studies of the relationship between pen gestures and speech. We illustrate the use of the SLOT platform by discussing the results of some early experiments. The first is an experiment on negotiation with a one-way mirror between the participants, and the second is an exploratory study of automatic recognition of spontaneous pen gestures. The results of these studies demonstrate the usefulness of the SLOT platform for conducting multimodal communication research in both human- human and human-computer interactions.

Communication↗
PubMed2004

Controversies in management of the neck in head and neck cancer.

As definitive external radiation and multimodality organ preservation strategies (eg, combined chemotherapy and radiation therapy ) improve, the role of surgery is being re-examined in the management of locally advanced head and neck cancer. Consensus regarding the use of neck dissections for complete responders and incomplete responders has yet to be achieved and the data are surprisingly controversial. A possible benefit from neck dissection after a complete response of the primary tumor after CCRT or definitive external radiation for advanced squamous cell carcinoma of the head and neck may only be anticipated in patients with persisting subclinical neck disease who have no other sites of disease. Some clinicians have even argued that the salvage rate for clinically detectable residual neck disease does not justify neck dissection. Randomized data addressing these questions and a trial addressing the accuracy of new imaging modalities, such as postchemotherapy and postradiation positron emission tomography scanning, across multiple institutions would be appropriate. As a department, we are aggressive in our treatment of isolated residual neck disease after CCRT or definitive external radiation and for patients initially diagnosed with N3 nodal disease. We are investigating the use of adjuvant neck brachytherapy at the time of neck dissection and we are pleased with our early results.

Antineoplastic Agents↗
PubMed2002

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001].

The standard primary therapy of advanced ovarian cancer consists of platinum derivatives in combination with paclitaxel. In a first report presented at this year's meeting of the American Society of Clinical Oncology (ASCO) docetaxel appeared to be as effective as paclitaxel in combination with carboplatin, while the toxicity profile present some advantages. The addition of a third drug to platinum-taxane-combination does not appear to improve the therapeutic index. According to the data of the ICON1- and ACTION-trial, carboplatin containing chemotherapies are associated with a significant benefit also in early ovarian cancer. Platinum-resistant disease remains a therapeutic challenge, since the available drugs display only limited activity of short duration. Some experimental data suggest evidence for a possible therapeutic role of small molecules that inhibit the epidermal growth factor receptor (OSI-774) or antisense oligonucleotides interfering with EGF-receptor signalling (ISIS 5132). Novel classes of chemotherapeutic agents, including the acylfulvenes and the epothilone-analogues warrant further study in this disease. Multimodal therapies combining cytotoxic agents with antibodies against CA 12-5 or metalloproteinase inhibitors have failed to demonstrate any survival benefit in patients with ovarian cancer. Despite significant progress in the last decade ovarian cancer remains the most lethal gynaecologic malignancy in women in most western countries. Further multicenter clinical studies are needed to better define new therapeutic options.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Genetic dissection of apoptosis and cell cycle control in response of colorectal cancer treated with preoperative radiochemotherapy.

BACKGROUND: In previous analyses we identified therapy-induced upregulation of the CDK inhibitor p21CIP/WAF-1 and consequently decreased tumor cell proliferation or loss of Bax as adverse factors for survival in rectal cancer treated with radiochemotherapy. Here, we address the individual role of p53 and its transcriptional targets, p21CIP/WAF-1 and Bax, on apoptosis induced by individual components of multimodal anticancer therapy, i.e. 5-fluorouracil (5-FU), ionising gamma-radiation (IR) and heat shock/hyperthermia. METHODS: We analysed tumor samples 66 patients with rectal carcinoma treated by a neoadjuvant approach with radiochemotherapy +/- heat shock/hyperthermia for the expression and mutation of p53 and the expression of p21CIP/WAF-1 and Bax. These data were correlated with the tumor response. The functional relevance of p53, p21CIP/WAF-1 and Bax was investigated in isogeneic HCT116 cell mutants treated with 5-FU, IR and heat shock. RESULTS: Rectal carcinoma patients who received an optimal heat shock treatment showed a response that correlated well with Bax expression (p = 0.018). Local tumor response in the whole cohort was linked to expression of p21CIP/WAF-1 (p < 0.05), but not p53 expression or mutation. This dichotomy of p53 pathway components regulating response to therapy was confirmed in vitro. In isogeneic HCT116 cell mutants, loss of Bax but not p53 or p21CIP/WAF-1 resulted in resistance against heat shock. In contrast, loss of p21CIP/WAF-1 or, to a lesser extent, p53 sensitized predominantly for 5-FU and IR. CONCLUSION: These data establish a different impact of p53 pathway components on treatment responses. While chemotherapy and IR depend primarily on cell cycle control and p21, heat shock depends primarily on Bax. In contrast, p53 status poorly correlates with response. These analyses therefore provide a rational approach for dissecting the mode of action of single treatment modalities that may be employed to circumvent clinically relevant resistance mechanisms in rectal cancer.

Antimetabolites, Antineoplastic↗
PubMed1993

Stereotactic insertion of intracerebral electrodes in the investigation of epilepsy.

Intracerebral electroencephalography is sometimes necessary in the pre-surgical evaluation of patients with drug-resistant epilepsy, in order to define the site(s) of seizure onset. Accurate depth electrode insertion would ideally require multimodal image integration, repetitive and non-invasive localization, assessment of positional accuracy and freedom in target and entry point selection. A method for the acquisition of the multimodal image stereotactic information, necessary for the precise targeting of the mesial temporal structures, and the operative technique used for the accurate placement of the intracerebral electrodes is described. The use of the Gill-Thomas (G-T) stereotactic repeat localizer offers the degree of temporal freedom during the data acquisition period of the electrode implantation procedure which leads to the advantage of an unhurried multi-image integration and targeting in any individual case combined with less discomfort for the patient. The integration of the G-T repeat localizing system with the existing components of the Cosman-Roberts-Wells (CRW-3) stereotactic system offers additional advantages. The target-centered arc-radius design allows complete freedom in the selection of the entry point, offers the possibility of multiple trajectories through the same entry point and permits a choice of either oblique or orthogonal lateral approaches, that are particularly useful for the electroencephalographic sampling of the posterior mesial temporal structures. The satisfactory localizing value of the technique and the additional advantage of easy confirmation of the positional accuracy of the electrodes during the postoperative period, using standard radiographic and magnetic resonance imaging studies, increases the potential of the technique for precise placement of depth electrodes during the pre-surgical evaluation of patients with epilepsy.

Amygdala↗