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PubMed2002

Effect of dissolution kinetics on feature size in dip-pen nanolithography.

We have investigated the effects of humidity, tip speed, and dwell time on feature size during dip pen nanolithography. Our results indicate a transition between two distinct deposition regimes occurs at a dwell time independent of humidity. While feature size increases with humidity, the relative increase is independent of dwell time. The results are described by a model that accounts for detachment and reattachment at the tip. The model suggests that, at short dwell times (high speed), the most important parameter controlling the feature size is the activation energy for thiol detachment.

Journal Article↗
PubMed1993

Voltage and temperature dependence of single K+ channels isolated from canine cardiac sarcoplasmic reticulum.

The temperature and voltage dependence of gating and conductance of sarcoplasmic reticulum K+ channels (S-R K+) isolated from adult canine hearts were studied using the reconstituted bilayer technique. Fusion of vesicles from this preparation frequently resulted in the incorporation of a single channel. Only bilayers into which a single S-R K+ channel had fused were studied. The three conductance states of the channel, fully open (O2), substate conductance (O1), and closed (C) were studied as a function of voltage (-50 to +50 mV) and temperature (16 to 37 degrees C). Permeation through the O1 state showed the same temperature dependence as the O2 state corresponding to an enthalpy of permeation of 4.1-4.2 kcal/mol, which is similar to that for K+ diffusion through water. As expected, increased temperature increased the frequency of gating transitions and shortened the average dwell time spent in any conductance state. Over the range of 25 to 37 degrees C, the average dwell time spent in the O1, O2, and C states decreased by 44 +/- 11, 36 +/- 13, and 78 +/- 7% (n = 3 to 4 channels), respectively. The ratio of probabilities between the various conductance states was not strongly temperature sensitive. Analysis of the voltage dependence of this channel was carried out at 37 degrees C and revealed that the dwell times of the O1 and O2 states were voltage insensitive and the probability ratio (PO2:PO1) was approximately 7 and was voltage insensitive. Nonlinear least-squares analysis of dwell times revealed that the closed state was biexponential and was thus composed of a fast (Cf) and a slow (C8) component.Tcf was voltage insensitive with an average value of 5.9 ms, whereas tau c was approximately two orders of magnitude slower and was voltage dependent. The voltage dependence of Cs was described by Tau c (ms) = exp(-0.025-(Vm (mV) - 250)).

Animals↗
PubMed2004

Efficacy and safety of reteplase for central venous catheter occlusion in patients with cancer.

PURPOSE: To evaluate the efficacy and safety of reteplase for central venous catheter (CVC) occlusion in patients with cancer. MATERIALS AND METHODS: An open-label, single-arm, prospective study was conducted. Reteplase (0.4 U) was instilled into each catheter lumen with a dwell time of 30 minutes in patients with cancer with a dysfunctional CVC. If the function of the catheter was not restored in 30 minutes, an additional dwell time of 30 minutes was allowed (a total of 60 minutes possible dwell time for the first dose). A second dose was repeated at 60 minutes after the first dose if catheter function was not restored (a total of 120 minutes for up to two doses). The primary efficacy outcome was the restoration of CVC function. RESULTS: Of 139 patients who received reteplase, the first-attempt success rate after a 30-minute dwell time was 66.9%. The cumulative success rates at 60, 90, and 120 minutes were 88.5%, 94.7%, and 94.7%, respectively. The variation of patient age, catheter age, CVC occlusion age, CVC type, number of lumen, or occlusion type was not associated with the efficacy of reteplase. There were no treatment-associated adverse events reported during the study period. CONCLUSION: Reteplase at 0.4-U dosing per catheter lumen is an effective and safe alternative that rapidly restores the patency of occluded CVCs in patients with cancer.

Adult↗
PubMedDate not supplied

Factors affecting bicarbonate transfer with bicarbonate-containing CAPD solution.

OBJECTIVE: To evaluate bicarbonate fluxes across the peritoneal membrane and bicarbonate gain in patients treated with continuous ambulatory peritoneal dialysis (CAPD) using dialysis solutions with different bicarbonate concentrations. PATIENTS AND DESIGN: Ninety-seven exchanges, using different dwell times and glucose and bicarbonate concentrations were performed in 43 stable CAPD patients. Dialysate effluent bicarbonate concentration and volumes were measured at different dwell times. Net dialytic bicarbonate gain was calculated. Patients' acid-base status was determined at the middle of the dwell. RESULTS: In prolonged dwells (6-12 hours) the dialysate effluent bicarbonate concentration correlated with arterial plasma bicarbonate concentration (F = 129, p < 0.0001), but not with ultrafiltration rate or dialysis solution bicarbonate concentration. In 4-hour dwells, effluent bicarbonate concentration correlated with both plasma bicarbonate concentration and ultrafiltration rate (F = 32.52, p < 0.0001 and F = 4.4, p < 0.05, respectively). The effluent bicarbonate concentration may be predicted from the patient's plasma bicarbonate concentration and net ultrafiltration rate for either a 4-hour or prolonged (6-12 hours) dwell time. Net bicarbonate gain by the patient correlated with ultrafiltration rate, plasma bicarbonate, and dialysis solution bicarbonate concentration (F = 100.56, p < 0.0001 at 4 hours and F = 108.08, p < 0.0001 at 6-12 hours), with the ultrafiltration rate being the predominant parameter. CONCLUSIONS: The effluent bicarbonate concentration is related to plasma bicarbonate concentration, with ultrafiltration playing a marginal role only during short dwells. However, the ultrafiltration rate has a profound effect on net patient bicarbonate gain. Multiple linear regression analysis allows the prediction of the effect of acid-base status, ultrafiltration, dwell time, and dialysis solution bicarbonate content on net patient bicarbonate gain. It seems that bicarbonate content in the CAPD dialysis solution should be progressively increased with increasing solution osmolality.

Acid-Base Equilibrium↗
PubMed1987

A model of ultrafiltration and glucose mass transfer kinetics in peritoneal dialysis.

We have investigated the variation with dwell time of dialysate volume and glucose concentration during continuous ambulatory peritoneal dialysis using a one-pool model. No assumption was made regarding the ultrafiltration rate that was calculated by the model. Results show that the volume ultrafiltered during dwell time is an increasing function of peritoneal membrane hydraulic permeability and a decreasing function of glucose mass transfer coefficient (MTC). For large MTC and low initial glucose concentration there is reabsorption of dialysate into the blood at large dwell times. For a 6 h dwell time, glycerol (92 daltons) is a more effective osmotic agent than glucose (198 daltons) at the same weight concentration. These results are in quantitative agreement with published clinical studies.

Biological Transport, Active↗
PubMedDate not supplied

Midline catheter use in the intensive care nursery.

PURPOSE: To describe the use of midline catheters in a Level IV, 48-bed NICU over a four-and-a-half-year period. DESIGN: Nonrandomized prospective review of data obtained for quality assurance monitoring. SAMPLE: 1,130 catheters inserted in 858 patients ranging in age at insertion from 1 to 249 days, 360-8,000 gm in weight, and 23-42 weeks gestational age at birth. OUTCOME VARIABLES: Catheter outcome data related to dwell times; patient characteristics; insertion site; and reason for removal, including failure related to infiltration, leaking, occlusion, dislodgment, infection, phlebitis, or malposition. RESULTS: There was no significant statistical difference in median catheter survival times related to weight or postconceptional age. Overall mean catheter dwell time was 8.7 days. Scalp was the most common insertion site (49 percent), and the site with the longest dwell time was the saphenous vein at the knee, which lasted a mean of 12.9 days. Elective removal represented 43 percent of all removals. Incidence of positive blood culture was 3.5 percent (0.41/1,000 catheter days), with the risk significantly higher if a central line was also in place.

Catheterization, Central Venous↗
PubMed2025

Mechanisms of enhanced or impaired DNA target selectivity driven by protein dimerization.

Successful DNA transcription demands coordination between proteins that bind DNA while simultaneously binding to one another to form dimers or higher-order complexes. For proteins with numerous DNA targets throughout the genome, measurements that report on their dwell time or occupancy thus represent a convolution over a population interacting with specific DNA, nonspecific DNA, or protein partners on DNA. Dimerization is known to add contacts that can help a single protein to stably bind DNA. However, we show here that dimerization can also impair measured dwell times and occupancy on target sequences because the population redistributes across DNA. We combine mass-action kinetic models of pairwise reversible reactions between proteins and DNA with theory and spatial stochastic simulations to isolate the role of dimerization on observed DNA dwell times, occupancy, and spatial distribution of proteins on DNA. Three key themes emerge: (i) Protein-protein interactions, in addition to protein-DNA interactions, can localize a protein to DNA, and relative binding rates can thus widely tune dwell times. (ii) Dimensional reduction achieved through nonspecific binding and subsequent 1D diffusion controls the order-of-magnitude of enhancements despite nucleosome barriers. (iii) Dimerization enhances selectivity for locally clustered targets and often impairs binding to widely-spaced targets by sequestration. Compared with ChIP-seq data, our model explains how the distribution of the essential GAF protein throughout the genome is highly selective for clustered targets due to protein interactions. This model framework predicts when even weak dimerization can redistribute and stabilize proteins on DNA as a necessary part of transcription.

DNA binding↗
PubMed1999

Gating kinetics of single large-conductance Ca2+-activated K+ channels in high Ca2+ suggest a two-tiered allosteric gating mechanism.

The Ca2+-dependent gating mechanism of large-conductance calcium-activated K+ (BK) channels from cultured rat skeletal muscle was examined from low (4 microM) to high (1,024 microM) intracellular concentrations of calcium (Ca2+i) using single-channel recording. Open probability (Po) increased with increasing Ca2+i (K0. 5 11.2 +/- 0.3 microM at +30 mV, Hill coefficient of 3.5 +/- 0.3), reaching a maximum of approximately 0.97 for Ca2+i approximately 100 microM. Increasing Ca2+i further to 1,024 microM had little additional effect on either Po or the single-channel kinetics. The channels gated among at least three to four open and four to five closed states at high levels of Ca2+i (>100 microM), compared with three to four open and five to seven closed states at lower Ca2+i. The ability of kinetic schemes to account for the single-channel kinetics was examined with simultaneous maximum likelihood fitting of two-dimensional (2-D) dwell-time distributions obtained from low to high Ca2+i. Kinetic schemes drawn from the 10-state Monod-Wyman-Changeux model could not describe the dwell-time distributions from low to high Ca2+i. Kinetic schemes drawn from Eigen's general model for a ligand-activated tetrameric protein could approximate the dwell-time distributions but not the dependency (correlations) between adjacent intervals at high Ca2+i. However, models drawn from a general 50 state two-tiered scheme, in which there were 25 closed states on the upper tier and 25 open states on the lower tier, could approximate both the dwell-time distributions and the dependency from low to high Ca2+i. In the two-tiered model, the BK channel can open directly from each closed state, and a minimum of five open and five closed states are available for gating at any given Ca2+i. A model that assumed that the apparent Ca2+-binding steps can reach a maximum rate at high Ca2+i could also approximate the gating from low to high Ca2+i. The considered models can serve as working hypotheses for the gating of BK channels.

Animals↗
PubMed2000

Upper extremity control in adults post stroke with mild residual impairment.

Motor control deficits in the upper extremity (UE) ipsilateral to the side of brain damage persist after stroke, but it is not known if the presence of these deficits is related to impairment of the contralateral UE. The purpose of this study was to investigate whether motor deficits are present in the ipsilateral UE when contralateral UE impairment is mild in adults with chronic stroke. Right-handed adults (10 controls, 10 right stroke, 10 left stroke) performed rapid continuous aiming movements to small and large targets. Using kinematic analysis, temporal measures of the movement were defined, including movement time (MT) and the three components of MT: acceleration, deceleration, and dwell time (i.e., time on target). Participants with right stroke had prolonged MT only with the left UE, primarily due to longer dwell times. Participants with left stroke had prolonged MT with both UEs as a result of longer dwell times. The results indicate that control deficits of the ipsilateral UE are evident in individuals with left but not right brain damage who have minimal impairment of the contralateral UE. These findings are consistent with the role of the left hemisphere in the control of both UEs.

Aged↗
PubMed2004

Molecular adsorption: early stage surface exploration.

In this study, the atomic force microscope has been employed in force spectroscopy mode to gain information on the interaction between long mucin molecules and a positively charged surface during the first few seconds of interaction. Recent studies have revealed that negatively charged mucin molecules introduced to a positively charged surface are kinetically trapped and bind very rapidly, assuming non-equilibrium conformations. This systematic study of surface dwell times has revealed that significant differences exist in mucin adsorption during the first three seconds of introduction to the surface and provides direct evidence of molecular rearrangement for several seconds before trapping occurs. Limited interactions were recorded at dwell times of less than one second, with increased molecular rearrangement observed between 1.5 and 2.25 s. Increasing the surface dwell time beyond this critical limit caused rupture of the tip-tethered mucin molecules during the retract cycle of the cantilever. All subsequent recorded events, at increased dwell times up to 3s, revealed events at much reduced distances from the point of contact between the mucin functionalised-cantilever and the positively charged surface.

Adsorption↗
PubMed2003

Incidence of central vein stenosis and occlusion following upper extremity PICC and port placement.

The purpose of this study was to determine the incidence of central vein stenosis and occlusion following upper extremity placement of peripherally inserted central venous catheters (PICCs) and venous ports. One hundred fifty-four patients who underwent venography of the ipsilateral central veins prior to initial and subsequent venous access device insertion were retrospectively identified. All follow-up venograms were interpreted at the time of catheter placement by one interventional radiologist over a 5-year period and compared to the findings on initial venography. For patients with central vein abnormalities, hospital and home infusion service records and radiology reports were reviewed to determine catheter dwell time and potential alternative etiologies of central vein stenosis or occlusion. The effect of catheter caliber and dwell time on development of central vein abnormalities was evaluated. Venography performed prior to initial catheter placement showed that 150 patients had normal central veins. Three patients had central vein stenosis, and one had central vein occlusion. Subsequent venograms (n = 154) at the time of additional venous access device placement demonstrated 8 patients with occlusions and 10 with stenoses. Three of the 18 patients with abnormal follow-up venograms were found to have potential alternative causes of central vein abnormalities. Excluding these 3 patients and the 4 patients with abnormal initial venograms, a 7% incidence of central vein stenosis or occlusion was found in patients with prior indwelling catheters and normal initial venograms. Catheter caliber showed no effect on the subsequent development of central vein abnormalities. Patients who developed new or worsened central vein stenosis or occlusion had significantly (p = 0.03) longer catheter dwell times than patients without central vein abnormalities. New central vein stenosis or occlusion occurred in 7% of patients following upper arm placement of venous access devices. Patients with longer catheter dwell time were more likely to develop central vein abnormalities. In order to preserve vascular access for dialysis fistulae and grafts and adhere to Dialysis Outcomes Quality Initiative guidelines, alternative venous access sites should be considered for patients with chronic renal insufficiency and end-stage renal disease.

Adolescent↗
PubMed2005

Visual search of mammographic images: influence of lesion subtlety.

RATIONALE AND OBJECTIVES: The goal of this study is to determine whether mammographic lesion subtlety influences the detection accuracy and visual search parameters of radiologists. MATERIALS AND METHODS: Six radiologists searched a set of 20 mammograms with at least two lesions per image (masses and/or microcalcifications). Eye position was recorded. False-negative (FN) and true-positive (TP) decisions were correlated with lesion subtlety and visual search parameters of time to first hit, total dwell time, and number of return fixations. RESULTS: Lesions with lower subtlety ratings were detected later in the search than more obvious ones (FN later than TP decisions). When subtler lesions were detected (TP), dwell time was longer than for more obvious lesions, but FN decisions received shorter total dwell. Subtler lesions, when detected (TP), received more total fixation clusters than more obvious ones, but FN decisions received fewer. CONCLUSION: Subtle mammographic lesions are associated with significantly different visual search parameters than obvious lesions, explaining in part why they are missed more often. Developing tools to improve lesion visibility may improve detection.

Analysis of Variance↗
PubMed1999

Influence of the preceding exchange on peritoneal equilibration test results: a prospective study.

The standard peritoneal equilibration test (PET) should be performed after a long overnight dwell, which is easily possible in continuous ambulatory peritoneal dialysis patients. However, for such a procedure, patients undergoing automated peritoneal dialysis or daily ambulatory peritoneal dialysis have to change their regimen and, in the case of high peritoneal transport rates, run the risk for fluid absorption. We compared dialysate to plasma ratios (D/P) of creatinine, blood urea nitrogen (BUN), phosphate, sodium, total protein, and albumin measured during PET after an 8- to 11-hour dry period (PET dry), after a preceding exchange with a long dwell time (PET standard), and immediately after tidal peritoneal dialysis (PET tidal). D/P ratios of creatinine, BUN, phosphate, and sodium at 2 and 4 hours were greater during PET dry compared with both PET standard and PET tidal. The quotient of dialysate glucose at 2 hours to dialysate glucose at time point 0 was significantly less in PET dry compared with both PET tidal and PET standard. During the first 2 hours of PET, the increase of D/P curves of creatinine and BUN, as well as phosphate, was significantly steeper in PET dry than PET tidal and PET standard. D/P ratios of albumin and protein were greatest in PET dry and least in PET tidal. There was a significant difference between all three PETs at 0, 2, and 4 hours of dwell time. PET curves were significantly steeper during PET dry compared with PET tidal in case of D/P protein (during the first 2 hours of dwell time) and D/P albumin (during the entire dwell time). Similar differences between the PET curves of protein and albumin were observed between PET dry and PET standard. These data clearly indicate a dry period before PET significantly influences the D/P ratios of small solutes, protein, and albumin measured during the test.

Adult↗
PubMed2002

Inverse planning for interstitial gynecologic template brachytherapy: truly anatomy-based planning.

PURPOSE: Commercially available optimization schemes generally result in an undesirable dose distribution, because of the particular shapes of tumors extending laterally from the tandem. Dose distribution is therefore manually obtained by adjusting relative dwell time values until an acceptable solution is found. The objective of this work is to present the clinical application of an inverse planning dose optimization tool for the automatic determination of source dwell time values in the treatment of interstitial gynecologic templates. METHODS AND MATERIALS: In cases where the tumor extends beyond the range of the tandem-ovoid applicator, catheters as well as the tandem are inserted into the paravaginal and parametrial region in an attempt to cover the tumor volume. CT scans of these patients are then used for CT-based dose planning. Dose distribution is obtained manually by varying the relative dwell times until adequate dose coverage is achieved. This manual planning is performed by an experienced physician. In parallel, our in-house inverse planning based on simulated annealing is used to automatically determine which of all possible dwell positions will become active and to calculate the dwell time values needed to fulfill dose constraints applied to the tumor volume and to each organ at risk. To compare the results of these planning methods, dose-volume histograms and isodose distributions were generated for the target and each organ at risk. RESULTS: This procedure has been applied for the dose planning of 12 consecutive interstitial gynecologic templates cases. For all cases, once the anatomy was contoured, the routine of inverse planning based on simulated annealing found the solution to the dose constraints within 1 min of CPU time. In comparison, manual planning took more than 45 min. The inverse planning-generated plans showed improved protection to organs at risk for the same coverage compared to manual planning. CONCLUSION: This inverse planning tool reduced the planning time significantly and produced improved plans with reduced dose to the organs at risk. Furthermore, the inverse planning approach improves the physician's control over treatment. The focus becomes the physician's prescription to the target and his or her compromise due to dose to normal structures.

Algorithms↗
PubMed1980

An analysis of perceptual and cognitive factors in radiographic interpretation.

Detection of small tumors in chest x-ray films was studied under tachistoscopic viewing conditions designed to stimulate single fixations varying in dwell time, found in free search. Two questions were asked: How much dwell time is required to detect a nodule (experiment 1)? How effective are peripheral inputs in the detection of a nodule (experiment 2)? Our findings indicate that a dwell time of 300 ms was sufficient to detect 85% of the nodules when they were viewed directly. Detection accuracy was reduced by one-half when the tumor was located 5 degrees from the axis of gaze. Taken together with data from eye movement experiments, these results provide useful estimates of perceptual and cognitive parameters of visual search.

Cognition↗
PubMed1995

Use of a modified peritoneal equilibration test to optimize solute and water clearance.

The standard peritoneal equilibration test (PET) characterizes the peritoneal transport of fluid, creatinine and urea. However, the applicability of the standard PET may be limited in patients on cycling peritoneal dialysis due to the choice of 2- and 4-h sampling times which exceed the usual dwell time of most patients on cycling peritoneal dialysis. We have performed a modified PET on seven pediatric dialysis patients in an effort to optimize dwell time to achieve maximal clearance of solutes and fluid. When compared with the standard PET, values obtained for dialysate/plasma urea and dialysate/plasma creatinine with the modified PET are significantly different. This resulted in an increased estimated creatinine clearance in five of seven and increased estimated urea clearance in six of seven patients. The modified PET is a more appropriate method for evaluation of peritoneal clearances in children as well as older patients who may require cycling peritoneal dialysis.

Adolescent↗
PubMedDate not supplied

Vascular endothelial growth factor (VEGF) levels in peritoneal dialysis effluent.

BACKGROUND: Long-term peritoneal dialysis (PD) patients who develop peritoneal ultrafiltration failure have an abnormally large number of capillaries and sclerotic changes in peritoneal biopsy. Peritoneal vascular endothelial growth factor (VEGF) production has been suggested to explain the higher levels in peritoneal effluent than in plasma. The high effluent VEGF levels have been related to peritoneal changes consisting of increased permeability to small molecules. To further analyze the relationship between peritoneal neoangiogenesis induced by VEGF and peritoneal transport, we studied peritoneal effluent VEGF levels in active PD patients. METHODS: VEGF levels were determined in serum and plasma, and in peritoneal effluent (PE) after 4, 8 and 15 h dwell times. RESULTS: PE VEGF levels were 58.6+/-33.7 pg/mL, with a mean VEGF D/P ratio of 0.45+/-0.29 (range 0.06-0.93). In low-transport patients (n = 7) this ratio did not differ from high-average ones (n=5) (0.48+/-0.3 and 0.41+/-0.1, NS). In multivariate analysis, the VEGF D/P ratio showed no correlation with the independent variables included in this study. VEGF levels were higher in 15 h than in 8 h effluent; so the VEGF D/P ratios were higher as well. Regression analysis showed a direct correlation between PEVEGF levels and dwell time (r: 0.57, p = 0.03), but not between VEGF D/P ratio and dwell time. PEVEGF levels directly correlated with effluent protein content. Regression analysis showed no correlation between PEVEGF levels and age, time on PD, days of peritonitis, urea and creatinine-mass transfer coefficients, ultrafiltration capacity, and accumulated glucose dose. Multivariate regression analysis showed correlation only between PEVEGF levels and dwell time, but not with the other independent variables. CONCLUSIONS: This study confirms that VEGF is present in fresh PE from PD patients at levels that suggest local production and filtration from plasma. Peritoneal effluent VEGF levels are not significantly associated with peritoneal functional parameters and background, and seem to be influenced by ultrafiltration in a dilution process. We believe that the role of VEGF in peritoneal pathophysiology is part of a complex relationship involving multiple peritoneal structures and other growth factors, including local counteracting factors for VEGF that regulate neoangiogenesis.

Dialysis Solutions↗
PubMed2001

Measurement of transit time of a remote after-loading high dose rate brachytherapy source.

Quantification of transit time of a remote after-loading high dose rate (HDR) brachytherapy source is important both for accurate treatment planning and for quality assurance checks. In this investigation, an HDR-1000 well ionization chamber and a precision electrometer are used to measure the transit time of the Ir-192 source of a Nucletron Micro-Selectron HDR brachytherapy unit. The charge generated both during source dwelling at a selected position in an endobronchial catheter inserted into the chamber and during source travel to this position from another location at a distance of 0.5 to 10 cm from it was measured. A linear regression analysis of the measured charge as a function of dwell time was made. The interdwell position transit time was calculated from the ratio of the charge intercept and the slope of the straight line obtained from the regression analysis. The values of the effective transit time, which is a combination of interdwell position transit time and dwell time error of the after-loading unit, were found to be 0.03 and 0.45 s for 0.5 and 10 cm separation between two dwell positions, respectively. The average time for 1 cm travel of the source between two dwell positions was found to be 0.022 s, resulting in an average speed of 45.5 cm/s. This simple procedure has the potential to be utilized for routine quality assurance check of the interdwell position transit time of any remote after-loading HDR brachytherapy source.

Brachytherapy↗