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PubMed2006

Third-harmonic generation in air by use of femtosecond radiation in tight-focusing conditions.

Third-harmonic generation (THG) in air in tight-focusing conditions is presented. Variation of the pulse duration supplied optimal conditions for THG by femtosecond pulses that varied in the range 110-1300 fs. We show that this third-harmonic generation was caused by Kerr-induced phase variations of fundamental and harmonic beams. Various characteristics (laser intensity, focusing conditions, pulse duration, air pressure, etc.) of THG in air were analyzed to optimize this process. The THG conversion efficiency of 795 nm, 300 fs radiation was 1 x 10(-3). The harmonic radiation did not show considerable disruption of its spectral and spatial distribution in tight focusing conditions for intensities as high as 5 x 10(14) W cm(-2).

Journal Article↗

PubMedDate not supplied

Delivery of clinical preventive services in family medicine offices.

BACKGROUND: This study aimed to elucidate how clinical preventive services are delivered in family practices and how this information might inform improvement efforts. METHODS: We used a comparative case study design to observe clinical preventive service delivery in 18 purposefully selected Midwestern family medicine offices from 1997 to 1999. Medical records, observation of outpatient encounters, and patient exit cards were used to calculate practice-level rates of delivery of clinical preventive services. Field notes from direct observation of clinical encounters and prolonged observation of the practice and transcripts from in-depth interviews of practice staff and physicians were systematically examined to identify approaches to delivering clinical preventive services recommended by the US Preventive Services Task Force. RESULTS: Practices developed individualized approaches for delivering clinical preventive services, with no one approach being successful across practices. Clinicians acknowledged a 3-fold mission of providing acute care, managing chronic problems, and prevention, but only some made prevention a priority. The clinical encounter was a central focus for preventive service delivery in all practices. Preventive services delivery rates often appeared to be influenced by competing demands within the clinical encounter (including between different preventive services), having a physician champion who prioritized prevention, and economic concerns. CONCLUSIONS: Practice quality improvement efforts that assume there is an optimal approach for delivering clinical preventive services fail to account for practices' propensity to optimize care processes to meet local contexts. Interventions to enhance clinical preventive service delivery should be tailored to meet the local needs of practices and their patient populations.

Family Practice↗

PubMed2000

Guideline implementation in the department of defense.

To improve the effectiveness of evidence-based clinical practice guidelines (CPGs), four other components of implementation are necessary. Together, they impressively optimize the process and outcomes of health care, and reduce undesirable variation of care. Aside from CPGs, the four components help make up a successful, long-term, facility-wide, comprehensive disease-management program. First, executive clinical and administrative leaders need to create the expectation and reveal hands-on commitment. Second, work-simplification tools are needed to accomplish the tasks more effectively and to encourage a path of least resistance. Third, useful, accurate metrics are needed to provide feedback for patients and health-care providers who need the most assistance. These metrics must be easily obtained, disseminated in near-real time, patient-specific, anonymous to others, and penalty free. Fourth, and most important, with nonmonetary compensation, this review addresses the question, "What's in it for all the passionate people who assist in the delivery of health care?"

Asthma↗

PubMed2006

Fluorescence in situ hybridization and comparative genomic hybridization.

This chapter discusses the complementary methodologies of fluorescence in situ hybridization and comparative genomic hybridization. Fluorescence in situ hybridization uses fluorescently labeled DNA probes (whole chromosomes, centromere, or locus-specific sequences) to visualize complementary DNA sequences in the target DNA (metaphase chromosomes or interphase nuclei). Comparative genomic hybridization is essentially a modified in situ hybridization, whereby the whole genome can be screened for gains and losses in a single experiment. Tumor and normal DNA are differentially fluorescently labeled and competitively co-hybridized to normal metaphase spreads. Both techniques require multiple steps in their preparation. These can be divided into preparation of the target, preparation of the probes, hybridization, post-hybridization washes, and image acquisition and analysis, each of which will be described in detail. Success of each experiment is dependent on all of these steps, but where steps are of critical importance to particular techniques, they will be highlighted, together with notes on how to optimize the process.

Breast Neoplasms↗

PubMed2001

T cell-mediated antigen presentation: a potential mechanism of infectious tolerance.

Differentiation of the T cell repertoire and the physiology of T cell-mediated antigen presentation are reviewed in relation to mechanisms of self-tolerance. Recent research has indicated that T cell development is a continual process that optimizes partial recognition of self as a homeostatic set-point. Specific T cell antigen recognition of partial agonists is intrinsically linked to expression of class II MHC glycoproteins on T cells. Even ligands that act as TCR antagonists in IL-2 production assays have sufficient agonistic strength to induce expression of class II MHC glycoproteins on T cells. Thus, the intrinsic self-reactivity of the T cell repertoire may promote T-APC activity in vivo and may explain why thymic and peripheral T cells express low but significant levels of class II MHC glycoproteins. T-APC activity induces extensive apoptosis among responder T cells, causes desensitization among surviving responders, and has been implicated in the adoptive transfer of tolerance in the Lewis rat model of experimental autoimmune encephalomyelitis. Overall, these findings support a relationship between the partial recognition of self MHC ligands, expression of class II MHC glycoproteins on mature peripheral T cells, tolerogenic T cell-mediated antigen presentation, and desensitization of pathogenic self-reactive T cells.

Animals↗

PubMed1975

Electrodecantation of serum proteins.

The sedimentation of albumin under the action of the electric and gravitational fields was determined as a function of time in discontinuous experiments in a rectangular cell, using serum with the albumin fraction stained blue. It was shown that even under the influence of strong electric fields, the upper boundary of the albumin layer fell no further than the mid-point of the cell. In continuous single-stage separation of gamma-globulin from other serum proteins, only about half the gamma-globulins can be obtained from the solution because it remains homogeneously distributed throughout the solution and is only free from albumin and other proteins in the upper half of the cell. In experiments with continuously operated triangular cells, the process was optimized to give gamma-globulin of 97.5% purity in a yield of 80%, at serum flow-through rates of up to 0.5 l/h in a block composed of 40 cells.

Animals↗

PubMed1994

[A needle electrode isolation amplifier for biomechanical studies].

In our laboratory for biomechanics, a new isolation amplifier was developed with which to record the electromyographic activity of muscles inaccessible to surface electrodes, in particular that of the rotator cuff. Our basic premisses were maximum safety for the patient or subject investigated, and optimal signal processing. These were achieved by a triple galvanic separation of the patient/subject from the battery power supply and the signal cables and by careful selection of the electronic components.

Electrodes↗

PubMed2005

Quantitative automated human chorionic gonadotropin measurement in urine using the Modular Analytics E170 module (Roche).

Ongoing demands on laboratory performance require optimization of processes. An obvious way to achieve this is to reduce manual labor in favor of automated methods. We describe the validation of an automated quantitative urine human chorionic gonadotropin (hCG) analysis on the Roche Modular E170 analyzer to replace the manual qualitative pregnancy test in urine. At urine hCG concentrations of 476, 45 and 11 U/L, we found inter-assay variation of 4.3%, 4.3% and 6.8% and average intra-assay variation of 3.0%, 2.6% and 3.0%, respectively. The analytical detection limit was 0.7 U/L. We did not detect any loss (due to degradation or adsorption) during a storage period of 5 days at 4 degrees C or at -20 degrees C. Recoveries of hCG in urine of a pregnant woman diluted with urine of a pre-menopausal non-pregnant woman (concentration range between 6 and 800 mU/L) were between 93% and 112% (y=0.997x-3.843, r 2 =0.999). Diluting a serum sample (hCG 42,000 U/L) with urine (negative for hCG) up to 8000-fold yielded a completely linear hCG response, indicating that the assay was not affected by the urine matrix. In a correlation study with 60 urine samples (of which 10 were of male origin), we did not find any discrepancies between results for the manual pregnancy test and the hCG test on the Roche Modular E170 (using a cutoff value of 50 U/L).

Analysis of Variance↗

PubMed2006

A behavioral homeostasis theory of habituation and sensitization: II. Further developments and predictions.

Habituation may be viewed as a decremental behavioral change to iterative stimuli of little immediate relevance. It is observed from protozoa to humans, indicating its evolutionary significance. If habituation is interpreted as the process of filtering out unimportant repetitive stimuli, then how should sensitization be interpreted? The 'behavioral homeostasis theory' of these two behaviors is based on the notion that organisms at a high level of 'alertness' prior to experiencing a new iterative stimulus will show a large initial response followed by a decrement (habituation) if the stimulus is of little significance. Conversely, the same organism at a low level of 'alertness' will show a small initial response to the same stimulus followed by an increase in 'alertness' and a larger response to the next stimulus (sensitization) in order to receive enough information to assess its significance. Circadian rhythmicity is hypothesized to play a role in determining 'alertness' to a new iterative stimulus at any given time. The level of responsiveness in initial habituaters and sensitizers, as an asymptote is approached, is a balance between being too 'alert' to an unimportant stimulus and missing other significant stimuli, and being too 'un-alert' and missing a change in the relevance of the present iterative stimulus. The concept of 'behavioral homeostasis' includes behaviors beyond habituation and sensitization across phylogeny. It includes instinctive as well as learned, and group as well as individual behavior. Such behavioral homeostatic processes to optimize detection and assessment of constantly occurring external stimuli are critical for organism survival. Clinical implications of this theory are also examined.

Animals↗

PubMed2006

Adhesive interactions between human neural stem cells and inflamed human vascular endothelium are mediated by integrins.

Understanding the mechanisms by which stem cells home precisely to regions of injury or degeneration is of importance to both basic and applied regenerative medicine. Optimizing regenerative processes may depend on identifying the range of molecules that subserve stem cell trafficking. The "rolling" of extravasating cells on endothelium under conditions of physiological flow is the first essential step in the homing cascade and determines cell adhesion and transmigration. Using a laminar flow chamber to simulate physiological shear stress, we explored an aspect of this process by using human neural stem cells (hNSCs). We observed that the interactions between hNSCs and tumor necrosis factor-alpha (TNF-alpha)-stimulated human endothelium (simulating an inflamed milieu) are mediated by a subclass of integrins--alpha2, alpha6, and beta1, but not alpha4, alphav, or the chemokine-mediated pathway CXCR4-stromal cell-derived factor-1alpha--suggesting not only that the mechanisms mediating hNSC homing via the vasculature differ from the mechanisms mediating homing through parenchyma, but also that each step invokes a distinct pathway mediating a specialized function in the hNSC homing cascade. (TNF-alpha stimulation also upregulates vascular cell adhesion molecule-1 expression on the hNSCs themselves and increases NSC-endothelial interactions.) The selective use of integrin subgroups to mediate homing of cells of neuroectodermal origin may also be used to ensure that cells within the systemic circulation are delivered to the pathological region of a given organ to the exclusion of other, perhaps undesired, organs.

Cell Adhesion↗

PubMed2005

Determination of 3-chloropropane-1,2-diol in liquid hydrolyzed vegetable proteins and soy sauce by solid-phase microextraction and gas chromatography/mass spectrometry.

Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) method was developed to determine 3-chloropropane-1,2-diol (3-MCPD) in hydrolyzed vegetable protein and Chinese soy sauce. The 3-MCPD was firstly derivativized with phenylboronic acid in aqueous solution at 90 degrees C for 10 min, then extracted by HS-SPME and finally detected with GC/MS, parameters related to both the derivative reaction and the HS-SPME process were optimized. The proposed method has a linear range of 0.0194-394 microg g(-1), a detection limit of 3.87 ng g(-1) (S/N = 3), and a precision of RSD = 7.5% (n = 5). Seventeen real samples, including four HVPs and thirteen soy sauce samples, were analyzed to examine the feasibility of the proposed procedure; with a concentration of 3-MCPD and acceptable recoveries at 0.71 microg g(-1) spiked levels were obtained. Being simpler, faster and more environmentally benign than the existing methods, this method is accurate and suitable for routine analysis.

Boronic Acids↗

PubMedDate not supplied

Aging effects on cadmium transport in undisturbed contaminated sandy soil columns.

Limited information is available on the effects of contaminant aging (i.e., the contact time of Cd with the soil) on Cd transport in soils. We conducted displacement experiments in which indigenous Cd and freshly applied Cd were leached simultaneously from undisturbed samples of three Spodosol horizons. Sorption of Cd was described using Freundlich isotherms, whereas transport was described as a convection-dispersion process. Parameter optimization analysis using a mobile-immobile transport model applied to nonsorbing tracer displacement data showed that 16 to 22% of the water in the columns was immobile. The low dimensionless mass transfer coefficients in the mobile-immobile model were indicative of diffusion-limited transfer between mobile and immobile water, and hence physical nonequilibrium. A two-site kinetic sorption model could be fitted closely to breakthrough curves of the non-aged Cd for three soil horizons. No conclusive evidence was found that contaminant aging in soil affects cadmium transport. On the one hand, predictions of aged Cd leaching, using parameters estimated from displacement experiments with nonaged Cd, differed from those for the aged Cd in the E horizon. On the other hand, no meaningful differences in transport behavior between aged and non-aged Cd were found for the humus Bh and Bh/C horizons. The two-site kinetic rate coefficient alphac was found to depend on water flux, further indicating that mass transfer between sorption sites and the liquid is limited by diffusion rather than by kinetic sorption.

Adsorption↗

PubMed2003

Automated high-throughput probe production for DNA microarray analysis.

DNA microarrays have become an established tool for gene expression profiling. Construction of these microarrays using immobilized cDNAs is a common experimental strategy. However, this is extremely laborious, requiring the preparation of hundreds or thousands of cDNA probes. To minimize this initial bottleneck, we developed a comprehensive high-throughput robotic system to prepare DNA probes suitable for microarray analysis with minimal user intervention. We describe an automated system using the MultiPROBE Nucleic Acid Purification Workstation to provide the liquid handling and other functions needed to optimize this process. We were able to carry out fully automated plasmid cDNA isolation, PCR assay setup, and PCR purification and also to direct the characterization and tracking of DNA probes during processing. Protocols began with the initial preparation of a plasmid DNA archive of bacterial stocks in parallel 96-well plates (192 samples/run) and continued through to the dilution and reformatting of chip-ready DNA probes in 384-well format. These and other probe production procedures and additional instrument systems were used to process fully a set of mouse cDNA clones that were then validated by differential gene expression analysis.

Animals↗

PubMed2004

Recent advances in the understanding of HIV-1 Vpu accessory protein functions.

HIV-1 encodes a number of accessory proteins, which are not commonly found in other retroviruses. These proteins, which include Vif, Vpr, Vpu and Nef, act as multifunctional adapters capable of recruiting and modulating basic host cell processes to optimize wide-ranging aspects of viral replication. This review describes our current understanding of how the Vpu accessory protein functions to modulate HIV-1 particle release and CD4 receptor expression during HIV-1 infection and underlines the potential opportunities afforded by this viral protein for therapeutic intervention.

Amino Acid Sequence↗

PubMed2002

Multivariate pharmaceutical profiling for drug discovery.

The field of pharmaceutical profiling in drug discovery is described. The pharmaceutical properties of drug candidates determine how much of the drug safely reaches the therapeutic target. Drug candidates often fail in discovery and development due to inadequate properties, resulting in lost opportunities and resources for developing new drugs. Pharmaceutical profiling assays have been developed and implemented to measure the properties of large numbers of drug candidates starting at the earliest stages of discovery. This information is used for informed decisions in drug candidate selection and synthetic optimization. A holistic process of parallel activity and property optimization has emerged in drug discovery. The assays, strategies, and data management associated with pharmaceutical profiling are discussed.

Animals↗

PubMedDate not supplied

A model for online interactive remote education for medical physics using the Internet.

BACKGROUND: Medical physics is a relatively small community but it spans great geographical distances, usually with a scarcity of experts whose expertise could greatly benefit students entering into the field. In addition there are many software systems for which an interactive education method would be most advantageous. OBJECTIVE: To develop a process to optimally use the Internet for real-time interactive remote education of medical physics and to present the experience of the study. METHODS: The project is a collaboration of the Department of Medical Physics at the Toronto-Sunnybrook Regional Cancer Centre in Canada and the Department of Radiology at the University of Malaya in Malaysia. A class of medical-physics graduate students at the University of Malaya attended lectures provided by lecturers in Toronto, using the Internet as the main tool of communication. RESULTS: The different methods that can be used to provide the real-time interactive remote education were explored, and various topics-including traditional classroom lectures as well as hands-on workshops-were also delivered. CONCLUSIONS: The concept of real-time interactive remote education is viable and holds promise for providing economical and practical tele-education to the medical physics community, but depends heavily on the availability of the Internet in many developing countries.

Computer Communication Networks↗

PubMed2006

Physical therapy treatment dose for nontraumatic neck pain: a comparison between 2 patient groups.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To classify patients with nonacute, nontraumatic neck pain according to the dominant impairment of spinal function, and to determine whether there were differences in the amount of treatment sessions required (treatment dose) to achieve a significant change in the patients disorder. BACKGROUND: Classification of patients with mechanical neck pain may be an important process in optimizing treatment prescription and evaluating treatment response. However, patient classification has not been used to consider possible differences in the amount of treatment sessions (treatment dose) required to achieve a significant change in the neck pain disorder. METHODS AND MEASURES: Ninety-two patients with nonacute, nontraumatic neck pain were classified into 2 groups, according to the dominant impairment of spinal function. Of the 77 patients who completed treatment, 63 (82%) were classified as having a "movement disorder," while the remainder was classified into a "loading disorder" group. Physical therapists who were blinded to the patient classification provided multimodal physical therapy treatment as considered appropriate and the patients were discharged when the optimal treatment response had been achieved. RESULTS: There was no difference in pain intensity or global disability level between the groups at baseline. Both groups achieved a significant improvement in neck pain and disability following treatment, and there was no significant difference between groups in the magnitude of the treatment response. The number of treatment sessions received by the loading group (mean +/- SD, 7.3 +/- 4.5) was significantly lower than the number received by the movement group (mean +/- SD, 11.5 +/- 5.9; 95% CI: -7.6 to -0.8; P<.01). Patients in the loading group were 2.4 times as likely to be discharged at any particular treatment session (95% CI: 1.1 to 4.1, P<.005) compared to those in the movement group. CONCLUSION: For patients with nontraumatic neck pain, classification according to impairment of spinal function may be a useful indicator of the number of physical therapy treatment sessions required to achieve a significant treatment response.

Adult↗

PubMed1996

Effects of barley variety and processing methods on feedlot steer performance and carcass characteristics.

An experiment was conducted to evaluate ammoniation and temper processing of two barley varieties of diverse types on feedlot cattle performance and diet digestibility. Steptoe (feed variety) and Klages (malting variety) barleys were processed as dry-rolled (DR); tempered and rolled (TR); tempered, ammoniated, and rolled (AR); and tempered, ammoniated, and fed whole (AW). Crossbred steers (n = 240, initial weight 266 kg) were blocked by weight and randomly assigned to one of eight treatments in a 2 x 4 factorial arrangement. Diets contained 30% barley (DM basis) for the growing phase and 85% (DM basis) for the finishing phase. Growing phase ADG and gain to feed (G/F) were less (P < .05) for AW than for DR, TR, and AR. Average daily gain was less (P < .05) for AW than for TR and AR in the finishing phase. There were no differences (P > .05) in ADG or G/F between DR, TR, and AR during growing or finishing phases. Gain to feed was greater (P < .05) for TR and AR than for AW but not for DR for the total trial. Hot carcass weight, longissimus muscle area, and kidney-pelvic-heart fat were greater (P < .05) for TR and AR than for AW. Total finishing diet ADF digestibility was greater (P < .05) for Steptoe than for Klages (40.5 vs 31.4%, respectively). The DR treatment had the lowest ADF digestibility, whereas AR had the greatest (P < .05). Results suggest that there were no differences in feedlot steer performance due to barley varieties of the same bulk density and that barley grain must be mechanically processed for optimal performance response rather than ammoniated and fed as whole grain.

Ammonia↗