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PubMed2002

Order and disorder in the nucleus.

Fluorescence in situ hybridization combined with three-dimensional microscopy has shown that chromosomes are not randomly strewn throughout the nucleus but are in fact fairly well organized, with different loci reproducibly found in different regions of the nucleus. At the same time, increasingly sophisticated methods to track and analyze the movements of specific chromosomal loci in vivo using four-dimensional microscopy have revealed that chromatin undergoes extensive Brownian motion. However, the diffusion of interphase chromatin is constrained, implying that chromosomes are physically anchored within the nucleus. This constraint on diffusion is the result of interactions between chromatin and structural elements within the nucleus, such as nuclear pores or the nuclear lamina. The combination of defined positioning with constrained diffusion has a strong impact on interactions between chromosomal loci, and appears to explain the tendency of certain chromosome rearrangements to occur during the development of cancer.

Animals↗

PubMed2001

Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter.

Effector T cells mediate adaptive immunity and immunopathology, but methods for tracking such cells in vivo are limited. We engineered knockin mice expressing IL-4 linked via a viral IRES element with enhanced green fluorescent protein (EGFP). Reporter T cells primed under Th2 conditions showed sensitive and faithful EGFP expression and maintained endogenous IL-4. After Nippostrongylus infection, reporter expression demonstrated the evolution of type 2 immunity from tissue lymphocytes and thence to lymph node CD4(+) T cells, which subsequently migrated into tissue. The appearance of EGFP(+) CD4(+) T cells in tissue, but not in lymph nodes, was Stat6-dependent. Transferred EGFP(+) CD4(+) T cells from infected animals conferred protection against Nippostrongylus to immunodeficient mice. These mice will provide a valuable reagent for assessing immunity in vivo.

Animals↗

PubMed2000

History of polar whaling: insights into the physiology of the great whales.

The sheer size and pelagic nature of the great whales has effectively precluded detailed studies of most of their physiological processes. The vast majority of all data for these species have come from anatomical studies conducted on specimens that were caught in commercial and native whaling operations. In both the polar regions, an incredible number of whales were hunted, but anatomical studies were not usually conducted until relatively recent times. However, the anatomical data that do exist provide a valuable insight into some of the physiological demands placed on the animals by their marine habitat. These include information on blubber and nutrition; baleen and feeding ecology; contaminant chemistry and tissue samples; diving chemistry and acoustics. Taken together, these anatomical data provide the only substantial information on how these animals dive and hunt. Recent breakthroughs in chemical techniques however, are providing even greater details on function (for example, fatty acid signature methods). Coupled with advanced methods for tracking these whales at sea (acoustic and satellite), future studies should provide significant new information on the general physiology of these difficult to study species.

Adipose Tissue↗

PubMed1998

Novel methods to monitor antigen-specific cytotoxic T-cell responses in cancer immunotherapy.

Monitoring cytotoxic T lymphocyte (CTL) responses to tumor antigens that have been defined at the molecular level has become essential to assess novel approaches to the specific immunotherapy of cancer. Nevertheless, because of the low affinity of the interactions between T-cell receptors and their ligands, there are no straightforward, well-standardized methods to meet this need. In this review, we describe several novel methods to track antigen-specific CTL responses.

Antigens, Neoplasm↗

PubMed2002

Serial registration of intraoperative MR images of the brain.

The increased use of image-guided surgery systems during neurosurgery has brought to prominence the inaccuracies of conventional intraoperative navigation systems caused by shape changes such as those due to brain shift. We propose a method to track the deformation of the brain and update preoperative images using intraoperative MR images acquired at different crucial time points during surgery. We use a deformable surface matching algorithm to capture the deformation of boundaries of key structures (cortical surface, ventricles and tumor) throughout the neurosurgical procedure, and a linear finite element elastic model to infer a volumetric deformation. The boundary data are extracted from intraoperative MR images using a real-time intraoperative segmentation algorithm. The algorithm has been applied to a sequence of intraoperative MR images of the brain exhibiting brain shift and tumor resection. Our results characterize the brain shift after opening of the dura and at the different stages of tumor resection, and brain swelling afterwards. Analysis of the average deformation capture was assessed by comparing landmarks identified manually and the results indicate an accuracy of 0.7+/-0.6 mm (mean+/-S.D.) for boundary surface landmarks, of 0.9+/-0.6 mm for landmarks inside the boundary surfaces, and 1.6+/-0.9 mm for landmarks in the vicinity of the tumor.

Algorithms↗

PubMed2000

Reproducibility of indices of axonal excitability in human subjects.

OBJECTIVES: Different indices of axonal excitability are now being measured in human subjects, both normal volunteers undergoing some test manoeuvre and patients with a variety of peripheral nerve disorders. The reproducibility of these indices has not previously been established, and was determined for cutaneous afferents in the median nerve of 12 healthy subjects, using threshold tracking techniques. METHODS: Refractoriness and supernormality were determined as the change in stimulus current required to produce a predetermined target potential when conditioned by a supramaximal stimulus at appropriate conditioning-test intervals. Strength-duration time constant was calculated from the threshold currents using unconditioned test stimuli of 0.1 ms and 1.0 ms. The effects of changes in membrane potential on these indices was assessed by applying subthreshold DC currents (from 50% depolarizing to 50% hyperpolarizing), using the reciprocal of threshold (i.e., 'excitability') as an indicator of membrane potential. The intraindividual reproducibility was determined by repeating the study on each subject up to 10 times. RESULTS: Refractoriness and supernormality were variable between subjects (mean +/- SD of 31.5 +/- 9.5% and 13.2 +/- 3.8%, respectively) and within subjects (coefficient of variation 0.2104 and 0.21849, respectively). TauSD showed even greater interindividual variability (499.2 +/- 115 micros) and intraindividual variability (coefficient of variation 0.2339). The slopes of relationships between each of the indices and axonal 'excitability' suggest that refractoriness is extremely sensitive to changes in excitability (0.9767 +/- 0.1907), tauSD less so (0.3766 +/- 0.1322), supernormality least (0.2223 +/- 0.1268). CONCLUSIONS: Under controlled conditions, refractoriness is the most sensitive and least variable of the indices of axonal excitability. However, small decreases in temperature greatly increase refractoriness but have little effect on tauSD. Given that 3 indices reflect different biophysical mechanisms, nodal and internodal, greater insight into the functional state of peripheral nerve axons will come when there are coherent changes in all 3 indices.

Adult↗

PubMed2005

Detecting single porphyrin molecules in a conically shaped synthetic nanopore.

We report here the first example of abiotic resistive-pulse sensing of a molecular (as opposed to a particle or macromolecular) analyte. This was accomplished by using a conically shaped nanopore prepared by the track-etch method as the sensing element. It is possible to sense the molecular analyte because the small diameter opening of the conical nanopore (approximately 4.5 nm) is comparable to the diameter of the analyte molecule (approximately 2 nm).

Journal Article↗

PubMed2004

Content analysis and key informant interviews to examine community response to the purchase, possession, and/or use of tobacco by minors.

The aim of this study was to identify and describe local ordinances in New Jersey that make it illegal for minors to purchase, possess, and/or use tobacco (PPU). A coding instrument was formulated and content analysis of each ordinance was conducted between March 1999 andJanuary 2002. Additionally, key informant interviews with community officials were conducted by telephone between September 2000 and February 2002 to collect qualitative information on implementation and enforcement. Content analysis of identified ordinances assessed when the ordinance was enacted, specific laws and clauses included, enforcing party, area of jurisdiction, and penalties associated with a citation. Key informant interviews assessed the catalyst for enacting the ordinance, penalties, enforcement activity, and method of tracking citations. As of January 2002, 48 municipalities in New Jersey had passed mandates banning minor purchase, possession, and/or use of tobacco. Of the 48 ordinances reviewed, 71% were passed during or after 1998. Nearly all of the ordinances (94%) included prohibited minor usage of tobacco, 77% prohibited minor possession of tobacco and 23% prohibited minor purchase of tobacco. In over 80% of communities, municipal police departments were responsible for enforcement. Two out of 35 communities reached for interview reported having a formal system for tracking enforcement or citations. The results illustrate that local PPU ordinances in New Jersey vary widely both in principle and in practice, suggesting that such ordinances may be too heterogeneous and lacking in cohesion to have any impact on youth smoking.

Adolescent↗

PubMed2000

Evidence for a link between global lightning activity and upper tropospheric water vapour

Tropospheric water vapour is a key element of the Earth's climate, which has direct effects as a greenhouse gas, as well as indirect effects through interaction with clouds, aerosols and tropospheric chemistry. Small changes in upper-tropospheric water vapour have a much larger impact on the greenhouse effect than small changes in water vapour in the lower atmosphere, but whether this impact is a positive or negative feedback remains uncertain. The main challenge in addressing this question is the difficulty in monitoring upper-tropospheric water vapour globally over long timescales. Here I show that upper-tropospheric water-vapour variability and global lightning activity are closely linked, suggesting that upper-tropospheric water-vapour changes can be inferred from records of global lightning activity, readily obtained from observations at a single location on the Earth's surface. This correlation reflects the fact that continental deep-convective thunderstorms transport large amounts of water vapour into the upper troposphere and thereby dominate the variations of global upper-tropospheric water vapour while producing most of the lightning on Earth. As global lightning induces Schumann resonances, an electromagnetic phenomenon in the atmosphere that can be observed easily at low cost, monitoring of these resonances might provide a convenient method for tracking upper-tropospheric water-vapour variability and hence contribute to a better understanding of the processes affecting climate change.

Journal Article↗

PubMed1995

Quantitative assessment of hyoid bone displacement from video images during swallowing.

Given the relationship between hyoid displacement and aspiration, a simple, accurate, clinically useful method for identification of reduced hyoid displacement is needed. The purpose of this investigation was to validate a quantitative method for clinically assessing hyoid bone movement during swallowing. Videofluoroscopic evaluations of 20 male subjects--10 who had been subjectively assessed as demonstrating normal hyoid displacement during swallowing, and 10 who had been subjectively assessed as demonstrating reduced displacement during swallowing--were analyzed. A video measuring gauge was used, and a software spreadsheet was developed to perform trigonometric calculations for determination of anterior/superior hyoid trajectories. Statistically significant differences were found between groups in both the anterior and superior directions of hyoid movement. No significant differences were found between liquid and paste swallows within groups. This method is simple in that it is necessary to identify only three to five points on two video images. Those values are then input onto a preprogrammed spreadsheet that automatically performs the necessary calculations. Although the present investigation focused on the movements of the hyoid bone during swallowing, this method of tracking displacement can be used for virtually any task or structure whose movements can be captured on videotape.

Deglutition Disorders↗

PubMed2005

The future of radioimmunotherapy: a PET perspective.

The future success of radioimmunotherapy (RIT) lies in building relationships between oncologists and nuclear medicine physicians. Communication between these specialists is key to the progress of radioimmunotherapy, and a team approach is required among all those involved in the process, not only for the benefit of the patient, but also for the success of research endeavors. Identification of the key questions regarding diagnosis and management of cancer must be formulated to design appropriate clinical trials incorporating radioimmunotherapy. The use of imaging modalities to conduct radiotracer studies may provide valuable information with regard to drug delivery and target specificity. One such approach is positron emission tomography (PET), a functional imaging modality with high sensitivity and specificity for tumor detection. The recent addition of hybrid PET/computed tomography, enabling biologic and anatomic whole-body imaging to be performed in one examination, has further facilitated the assignment of biologic abnormalities to anatomic structures. The most widely used radiotracer for PET is 18 F-fluorodeoxyglucose; however, fluorodeoxyglucose is a relatively nonspecific tracer. Novel, more specific tracers are being designed to assess cell proliferation. Radiolabeled non-catabolized derivatives of thymidine that are incorporated into cellular DNA are undergoing clinical trials for diagnostic efficacy using PET. In vivo anatomic micro-imaging technologies, such as microPET, microcomputed tomography, and micro-magnetic resonance imaging, enable the assessment of metabolism, cell communication, and gene expression in animal models. Fast-tracking imaging methods through translational research to human use is critical if imaging is to aid in the delivery of optimal cancer treatments. This article presents an overview of the way in which imaging may facilitate the evaluation of new treatment modalities to advance patient treatment and care.

Humans↗

PubMed1980

[Medical radiography with fast neutrons (author's transl)].

For physical reasons, radiography by neutrons produces radiographs which are quite different from x-ray images. Biological objects can be transradiated only by fast neutrons. Selective simultaneous recording of neutron images is accomplished best by using cellulose nitrate (CN) foils, used with a track etching method in order to exclude thermal neutrons and gamma quanta. A neutron-radiography set-up in connection with a research reactor is described, as well as optimal conditions for developing the CN foils and the optical display of the resultant image. Image quality of the individual CN foil is characterised by minimal interior unsharpness (35 mu) and a small range of blackening when compared with radiographic film (about 1). Image contrast can be increased by the use of many foils. In addition, this results in a reduction of maximal radiation dose to below 10 rem. Study of isolated spines has shown that fat and necrotic tumours can be demonstrated by neutron radiography without being superimposed by calcium-containing bone, even if these changes cannot be seen on a x-ray radiograph because of the regular bone structure. It appears that neutron radiography can be superior to conventional radiography for the diagnosis of abnormalities with bones, or of areas surrounded by bone. The use of neutron radiography in patients can, at the moment, only be justified for individuals undergoing neutron therapy for the treatment of tumours.

Fast Neutrons↗

PubMed2003

Hospital use and survival among Veterans Affairs beneficiaries.

BACKGROUND: Initiatives to reduce hospital care were part of the reorganization of the Department of Veterans Affairs (VA) medical care system undertaken in the mid-1990s. We examined changes in the use of VA health services and survival from 1994 through 1998 among VA beneficiaries with serious chronic diseases. We postulated that if access to hospital care was reduced too much, or if decreased hospital use was not offset by improvements in ambulatory care, urgent care visits would increase or survival rates would fall. METHODS: We tracked changes in risk-adjusted VA bed-day rates, rates of medical visits, rates of visits for testing and consultation, and rates of urgent care visits per patient-year among VA beneficiaries in nine disease cohorts (a total of 342,300 beneficiaries). Trends in non-VA hospital use by VA beneficiaries 65 years of age or older who were enrolled in fee-for-service Medicare were also studied. VA and Medicare vital-status data were used to calculate one-year survival rates. RESULTS: From 1994 through 1998, VA bed-day rates fell by 50 percent, rates of medical-clinic visits and visits for testing and consultation increased moderately, and rates of urgent care visits fell by 35 percent. The sharp decline in the use of VA hospitals was not compensated for by increases in the use of Medicare-reimbursed non-VA hospital care by veterans eligible for both VA care and Medicare, and the use of non-VA hospitals actually declined in four cohorts. The survival rates were essentially unchanged over the study period. CONCLUSIONS: The marked decline in VA hospital use from 1994 through 1998 did not curtail access to needed services and was not associated with serious consequences for chronically ill VA beneficiaries.

Chronic Disease↗

PubMed2006

Ionic conduction, rectification, and selectivity in single conical nanopores.

Modern track-etching methods allow the preparation of membranes containing a single charged conical nanopore that shows high ionic permselectivity due to the electrical interactions of the surface pore charges with the mobile ions in the aqueous solution. The nanopore has potential applications in electrically assisted single-particle detection, analysis, and separation of biomolecules. We present a detailed theoretical and experimental account of the effects of pore radii and electrolyte concentration on the current-voltage and current-concentration curves. The physical model used is based on the Nernst-Planck and Poisson equations. Since the validity of continuum models for the description of ion transport under different voltages and concentrations is recognized as one of the main issues in the modeling of future applications, special attention is paid to the fundamental understanding of the electrical interactions between the nanopore fixed charges and the mobile charges confined in the reduced volume of the inside solution.

Biological Transport↗

PubMedDate not supplied

Organizing language intervention relative to the client's personal experience: a clinical case study.

An analysis is presented of two different therapeutic activities designed for a profoundly deaf adult with cerebral palsy, DP. The study draws on techniques of qualitative methodology to identify elements that contribute to effective intervention practices for DP. Results indicate that therapeutic materials and activities must first of all be relevant to the client's needs, interest, and personal experience to be maximally effective. The results are consistent with recent research on language and language development, particularly the cognitive linguistic view that our linguistic knowledge is rooted in our experience with the world (Kecskes). These results are also consistent with a "socially valid and consumer focused method of tracking outcome" (Simmons-Mackie and Damico) in that language intervention must typically capture the personal experience of communicatively disordered individuals. Specific recommendations are made for optimizing language intervention.

Adult↗

PubMed1986

Biological effectiveness of low energy protons. I. Survival of Chinese hamster cells.

The biological effectiveness of monoenergetic protons was investigated with the track-segment method. Protons were accelerated by a Tandem Van de Graaff accelerator and their final energies were 3.0 and 7.4 MeV. The biological system used was Chinese hamster V-79 cells and their survival ability following proton irradiation was investigated. Cobalt-60 gamma-rays were used as reference radiation to assess proton relative biological effectiveness (RBE). Survival curves were obtained for the gamma-ray and proton irradiations, and the relation S = exp (-alpha D-beta D2) was fitted to the data and the parameters alpha and beta were determined. The RBE values, calculated on the basis of the mean inactivation dose D and other pertinent parameters, were found to be 1.7 +/- 0.1 and 2.8 +/- 0.2 for 7.4 and 3.0 MeV protons, respectively. Comparisons were made with the results published by other investigators and it was concluded that in this low energy range the biological effectiveness increases substantially with decreasing proton energy.

Animals↗

PubMed2006

Techniques and considerations for determining isoinertial upper-body power.

Power is an integral aspect of many sports. Although power output of the lower body is often measured during jumping and cycling movements, much less is known about power as pertains to the upper body musculature. Recently, isoinertial methods--with constant gravitational load--of power testing have become common, but little is known of the reliability and criterion validity of these tests as they pertain to sport performance. In addition, the varied methodology makes a lucid model more evasive. The aims of this review are to examine the various methods of assessing upper body power, to establish its role in predicting athletic performance, and to assess the body of literature that has assessed power output of the upper extremities by isoinertial methods. To our knowledge, only two studies on isoinertial upper-body power have shown a direct correlation to sporting ability (Baker, 2001; Baker et al., 2001); therefore, many unanswered questions exist as to the efficacy of these tests as predictors of athletic ability or as a method to track athletes' training over time. From this review we hope to allow the sport coach to assess the overall utility of these tests in terms of availability, safety and external validity.

Arm↗

PubMed2001

Tracking issue attention: specifying the dynamics of the public agenda.

While interest in issues shifts daily, tracking these changes is currently done by multiple surveys, which are conducted months apart. In this article, we adapt political tracking poll methods to model the functional form of issue attention changes through three phases, including equilibrium, developing interest, and decline. We find that opinions do follow discernible cycles. Further, we test and find strong support for the "boredom" explanation that reactions to external events that are brought to the attention of the public through the media are much greater during the developing interest phase than the saturation phase. The evidence gathered from the newly adapted method has implications for modeling the issue-attention cycle and testing the effects of media coverage and external events on public interest in issues.

Journal Article↗