MicroCT Imaging of Heart Valve Tissue in Fluid.

BACKGROUND: Heart valve computational models require high quality geometric input data, commonly obtained using micro-computed tomography. Whether in the open or closed configuration, most studies utilize dry valves, which poses significant challenges including gravitational and surface tension effects along with desiccation induced mechanical changes. OBJECTIVE: These challenges are overcome by scanning in a stress-free configuration in fluid. Utilizing fluid backgrounds however reduces overall contrast due to the similar density of fluid and tissue. METHODS: The work presented here demonstrates imaging of the mitral valve by utilizing an iodine-based staining solution to improve the contrast of valve tissue against a fluid background and investigates the role of stain time and concentration. RESULTS: It is determined that an Olea europaea oil bath with a relatively high concentration, short stain time approach produces high quality imagery suitable for creating accurate 3D renderings. CONCLUSIONS: Micro-CT scanning of heart valves in fluid is shown to be feasible using iodine staining techniques.

Impact of motivational interviewing on engagement in a parent-exclusive paediatric obesity intervention: randomized controlled trial of NOURISH+MI.

BACKGROUND: Attrition and treatment adherence are notorious challenges in paediatric obesity interventions. OBJECTIVE: To evaluate if brief, pretreatment motivational interviewing (MI) can improve retention (at baseline, post-assessment and follow-up assessment) and adherence (i.e. attendance) in a parent-exclusive paediatric obesity intervention. METHODS: MI was implemented with parents as an adjunct to a larger randomized controlled trial of Nourishing Our Understanding of Role-modeling to Improve Support and Health (NOURISH+ ), a parent intervention for children with overweight ages 5-11 years. Parents (N = 112) were randomized to receive two MI sessions (one telephone and one in person) or reminder calls. RESULTS: Parents (91% women; 52% African American) who completed one telephone MI session were more likely to attend baseline (74%) compared with parents who received reminder calls only (53%, p < .001). After a second MI session, there were no group differences in treatment initiation (p > .05). Treatment attendance, post or 4-month follow-up assessment completion did not differ between conditions (p > .05). CONCLUSION: One MI session implemented prior to treatment can improve baseline attendance; a second MI session did not enhance these effects. A single-session telephone-based MI pretreatment might be a cost and time-effective strategy to enhance recruitment efforts. Further strategies to address retention and treatment attendance are needed.

Impact of motivational interviewing on outcomes of an adolescent obesity treatment: results from the MI Values randomized controlled pilot trial.

The aim of this study is to examine outcomes from MI Values, a motivational interviewing (MI) intervention implemented adjunctive to obesity treatment. Adolescents (n = 99; 73% African American; 74% female; mean body mass index [BMI] percentile = 98.9 ± 1.2) were randomized to receive two MI sessions or education control. All adolescents participated in structured behavioural weight management treatment. Baseline, 3- and 6-month assessments of anthropometrics, dietary intake and physical activity were obtained. Both groups had significant reductions in BMI z-scores and energy intake and increased physical activity at 3 and 6 months (P < 0.05). MI participants reported greater reductions in 3-month energy intake compared with controls. Participation in MI is associated with reduction in energy intake, consistent with better adherence to dietitian visits previously reported from MI Values. MI might be an effective adjunct to adolescent obesity treatment; future research is needed to determine if motivational interviewing can enhance BMI outcomes, via greater adherence to behavioural intervention.

A NEW SEMI-EMPIRICAL AMBIENT TO EFFECTIVE DOSE CONVERSION MODEL FOR THE PREDICTIVE CODE FOR AIRCREW RADIATION EXPOSURE (PCAIRE).

The Predictive Code for Aircrew Radiation Exposure (PCAIRE) is a semi-empirical code that estimates both ambient dose equivalent, based on years of on-board measurements, and effective dose to aircrew. Currently, PCAIRE estimates effective dose by converting the ambient dose equivalent to effective dose (E/H) using a model that is based on radiation transport calculations and on the radiation weighting factors recommended in International Commission on Radiological Protection (ICRP) 60. In this study, a new semi-empirical E/H model is proposed to replace the existing transport calculation models. The new model is based on flight data measured using a tissue-equivalent proportional counter (TEPC). The measured flight TEPC data are separated into a low- and a high-lineal-energy spectrum using an amplitude-weighted 137Cs TEPC spectrum. The high-lineal-energy spectrum is determined by subtracting the low-lineal-energy spectrum from the measured flight TEPC spectrum. With knowledge of E/H for the low- and high-lineal-energy spectra, the total E/H is estimated for a given flight altitude and geographic location. The semi-empirical E/H model also uses new radiation weighting factors to align the model with the most recent ICRP 103 recommendations. The ICRP 103-based semi-empirical effective dose model predicts that there is a ∼30 % reduction in dose in comparison with the ICRP 60-based model. Furthermore, the ambient dose equivalent is now a more conservative dose estimate for jet aircraft altitudes in the range of 7-13 km (FL230-430). This new semi-empirical E/H model is validated against E/H predicted from a Monte Carlo N-Particle transport code simulation of cosmic ray propagation through the Earth's atmosphere. Its implementation allows PCAIRE to provide an accurate semi-empirical estimate of the effective dose.

Motivational interviewing targeting diet and physical activity improves adherence to paediatric obesity treatment: results from the MI†Values randomized controlled trial.

BACKGROUND: Adherence is a challenge in obesity treatment. Motivational interviewing (MI) may promote patient adherence. MI Values is a randomized controlled trial of MI implemented as an adjunct to an adolescent obesity treatment [Teaching Encouragement Exercise Nutrition Support (T.E.E.N.S.)]. OBJECTIVE: Assess effects of MI Values on T.E.E.N.S. attrition and adherence. METHODS: Participants were randomized to MI (n = 58) or control (n = 41). At weeks 1 and 10, MI participants had brief MI sessions; controls viewed health education videos. All participants continued with T.E.E.N.S. (biweekly dietitian and behavioural support visits; 3 times per week supervised physical activity). Assessments were repeated at baseline, 3 and 6 months. T-tests and chi-square analyses examined T.E.E.N.S. attrition and adherence by group. RESULTS: Adolescents (N = 99) were primarily African-American (73%) females (74%); age = 13.8 ± 1.8 years, body mass index percentile = 98.0 ± 1.2. Compared with controls, MI participants had greater 3-month adherence overall (89.2% vs. 81.0%, P = 0.040), and to dietitian (91.3% vs. 84.0%; P = 0.046) and behavioural support (92.9% vs. 85.2%; P = 0.041) visits, and greater 6-month adherence overall (84.4% vs. 76.2%, P = 0.026) and to behavioural support visits (87.5% vs. 78.8%, P = 0.011). CONCLUSIONS: MI enhanced adherence to this obesity intervention. MI Values is the first study to examine the impact of MI on treatment adherence among obese, primarily African-American adolescents.

Lupus anticoagulant, antiphospholipid syndrome and cardiac surgery.

The presence of lupus anticoagulant and the related condition antiphospholipid syndrome present a challenge in cardiac surgery where measured anticoagulation may not reflect the in vivo patient status of hypercoagulation. We report the successful management of a patient with lupus anticoagulant presenting for aortic valve replacement and coronary revascularisation. We used heparin for anticoagulation, specialised additional tests of anticoagulation and a reduced protamine dose. We also used tranexamic acid. The clinical problems with anticoagulation in patients with lupus anticoagulant include anticoagulant choice, measurement of adequate anticoagulation, antifibrinolytic usage, protamine dosing and blood product transfusion.

Monte Carlo simulation of a PhosWatch detector using Geant4 for xenon isotope beta-gamma coincidence spectrum profile and detection efficiency calculations.

A simulation tool has been developed using the Geant4 Toolkit to simulate a PhosWatch single channel beta-gamma coincidence detection system consisting of a CsI(Tl)/BC404 Phoswich well detector and pulse shape analysis algorithms implemented digital signal processor. The tool can be used to simulate the detector's response for all the gamma rays and beta particles emitted from (135)Xe, (133m)Xe, (133)Xe, (131m)Xe and (214)Pb. Two- and three-dimensional beta-gamma coincidence spectra from the PhosWatch detector can be produced using the simulation tool. The accurately simulated spectra could be used to calculate system coincidence detection efficiency for each xenon isotope, the corrections for the interference from the various spectral components from radon and xenon isotopes, and system gain calibration. Also, it can generate two- and three-dimensional xenon reference spectra to test beta-gamma coincidence spectral deconvolution analysis software.

Development of a predictive code for aircrew radiation exposure.

Using the empirical data measured by the Royal Military College with a tissue equivalent proportional counter, a model was derived to allow for the interpolation of the dose rate for any global position, altitude and date. Through integration of the dose-rate function over a great circle flight path or between various waypoints, a Predictive Code for Aircrew Radiation Exposure (PCAire) was further developed to provide an estimate of the total dose equivalent on any route worldwide at any period in the solar cycle.

Measurement and modelling of radioxenon plumes in the Ottawa Valley.

Since 2001 a real-time radiation monitoring network of Canadian nuclear facilities and major population centres has been implemented for response to nuclear incidents including a possible terrorist attack. Unshielded NaI(Tl) spectroscopic detectors are employed to measure gamma radiation from airborne radioactivity and radioactivity deposited on the ground. These detectors are composed of a standard 3''x3'' cylindrical NaI(Tl) spectrometers with data storage and integrated telemetry. Some of the detectors have been deployed in the Ottawa Valley near Chalk River Laboratories and Ottawa, which has a complex radioxenon environment due to the proximity of nuclear power reactors, and medical isotope facilities. Although not a health threat, these releases have provided an opportunity for the Canadian Meteorological Centre and the Commissariat à l'Energie Atomique to validate their meteorological models. The meteorological models of the two organizations are in good agreement on the origin and the source terms of these releases.

Automated radioxenon monitoring for the comprehensive nuclear-test-ban treaty in two distinctive locations: Ottawa and Tahiti.

In preparation for verification of the Comprehensive Nuclear-Test-Ban-Treaty, automated radioxenon monitoring is performed in two distinctive environments: Ottawa and Tahiti. These sites are monitored with SPALAX (Systeme de Prelevement d'air Automatique en Ligne avec l'Analyse des radioXenons) technology, which automatically extracts radioxenon from the atmosphere and measures the activity concentrations of (131m,133m,133,135)Xe. The resulting isotopic concentrations can be useful to discern nuclear explosions from nuclear industry xenon emissions. Ambient radon background, which may adversely impact analyser sensitivity, is discussed. Upper concentration limits are reported for the apparently radioxenon free Tahiti environment. Ottawa has a complex radioxenon background due to proximity to nuclear reactors and medical isotope facilities. Meteorological models suggest that, depending on the wind direction, the radioxenon detected in Ottawa can be characteristic of the normal radioxenon background in the Eastern United States, Europe, and Japan or distinctive due to medical isotope production.

High glycemic index carbohydrate diet alters the diurnal rhythm of leptin but not insulin concentrations.

Morning serum leptin values in humans are inconsistently altered by diet, and the molecular mechanisms controlling the diurnal leptin pattern remain unexplained. We determined whether leptin values after meals or the leptin diurnal pattern was altered by the type of carbohydrate (CHO) ingested in diets containing either 20% or 30% fat. In a randomized, crossover study design, nine healthy lean adults ate one of four isocaloric diets for 8 days. Diets contained 15% protein: A, high glycemic index (GI) CHO, 30% fat; B, low GI CHO, 30% fat; C, high GI CHO, 20% fat; and D, low GI CHO, 20% fat. Serum glucose, insulin, and leptin were measured at intervals on Day 8 for 24 hr, and on Day 9 during an oral glucose tolerance test (GTT). Although the 24-hr glucose and insulin profiles did not differ with the diets, diets A and C altered the serum leptin diurnal pattern. In contrast to the usual evening rise in leptin concentration, which begins after 2200 hr, diets A and C caused a rise in leptin beginning at 1300 hr. The area under the curve for leptin between 1230 and 2400 hr was 17% greater for diets A and C. During the GTT, leptin concentrations were similar for each diet. These results suggest that the pattern and amount of leptin secretion may be altered by high GI CHO or the simple sugar content of the diet, unrelated to differences in insulin concentration, that high GI foods may have little or no effect on serum insulin in the context of a mixed meal, and that a single 0800-hr leptin value may not be sufficient to reveal a diet-induced change in leptin secretion

Inhibition of collagen synthesis with prolyl 4-hydroxylase inhibitor improves left ventricular function and alters the pattern of left ventricular dilatation after myocardial infarction.

Background- Left ventricular (LV) remodeling after myocardial infarction (MI) is associated with fibrosis, dilatation, and dysfunction. We postulated that prevention of fibrosis after MI with a prolyl 4-hydroxylase inhibitor (P4HI) would preserve LV function and attenuate LV enlargement. Methods and Results- Adult female rats (200 to 250 g) had experimental MI and were then randomized to treatment with P4HI (MI-FG041, n=29) or vehicle (MI-control, n=29) 48 hours after MI for 4 weeks in 2 phases. Echocardiograms were performed weekly with a 15-MHz linear transducer, and at 4 weeks, collagen isoform determinations and in vivo hemodynamics were performed. At randomization, the infarct size and LV function and size were similar in MI-FG041 and MI-control but significantly different from shams (n=9). At week 4, the LV function in MI-FG041 was significantly better than in MI-controls (fractional shortening 21% versus 16%, P=0.01; fractional area change 30% versus 19%, P=0.002; ejection fraction 35% versus 23%, P=0.001). In the FG041 group, LV area in systole was less (P<0.05), the dP/dt(max) after isoproterenol was higher (P<0.05), and types I and III collagen in noninfarcted LV were less than in MI-control. The hydroxyproline/proline ratio was increased by 64% in MI-control and reduced to the sham value in MI-FG041 rats. In the scar tissue, it was reduced by 24% in MI-FG041. Conclusions- This study demonstrates that prevention of interstitial fibrosis with a P4H inhibitor alters the pattern of LV enlargement and produces partial recovery of LV function after MI.

T-cell responses to mitogens in atomic bomb survivors: a decreased capacity to produce interleukin 2 characterizes the T cells of heavily irradiated individuals.

Significant decreases in the fraction of lymphocytes that are CD4(+) and increases in serum levels of some classes of immunoglobulin have been reported to occur in atomic bomb (A-bomb) survivors and in victims of the Chernobyl nuclear plant accident. To investigate the long-term effects of nuclear radiation on cellular immunity in more detail, we used limiting dilution assays with peripheral blood mononuclear cell preparations to analyze the T-cell responses of 251 A-bomb survivors exposed to less than 0.005 Gy and 159 survivors exposed to more than 1.5 Gy. The percentages of CD2-positive cells that were capable of proliferating in response to phytohemagglutinin (PHA) in the presence of exogenous interleukin 2 (IL2) did not differ substantially between distally exposed and more heavily exposed survivors. The heavily exposed survivors appeared to possess fewer T cells that were capable of proliferating in response to concanavalin A (Con A) or of producing interleukin 2. Assuming that CD4 T cells were the ones primarily responsible for producing IL2 in response to Con A, we were able to estimate how many cells in any given CD4 T-cell population were actually producing IL2. The results indicated that peripheral blood samples from heavily exposed survivors contained significantly fewer IL2-producing CD4 T cells than did similar samples from distally exposed survivors, indicating that significant exposure to A-bomb radiation may have a long-lasting negative effect on the capacity of CD4 T-cell populations to produce IL2.

Is the technically limited echocardiographic study an endangered species? endocardial border definition with native tissue harmonic imaging and Optison contrast: a review of 200 cases.

OBJECTIVE: Our goal was to determine whether contrast adds diagnostic value to both fundamental and native tissue harmonic imaging (NTHI) for endocardial border definition. METHODS: Two hundred consecutive patients who underwent stress echocardiography imaging were studied in either fundamental (n = 52) or NTHI mode (n = 148) with an Acuson Sequoia echocardiographic system. Contrast agent (Optison) was administered (0.5 to 1 mL) for enhancement of endocardial borders. Two- and 4-chamber views were analyzed before and after administration of contrast at peak stress for grading of 5 endocardial border segments. Scores from 0 to 5 were assigned to each study for all the images both before and after contrast (0 = 0 segments completely visualized; 5 = 5 segments completely visualized). RESULTS: The use of Optison contrast significantly enhanced border definition when imaging was performed in either fundamental or NTHI mode. Addition of contrast resulted in better endocardial border definition in fundamental mode (4.1 + or - 1.0 versus 2.3 + or - 1.3, P <.001). However, in NTHI mode, the presence of contrast resulted in enhanced definition of endocardial border compared with its absence (4.8 + or - 0.5 versus 3.3 + or - 1.1, P <.001). The combination of NTHI and contrast resulted in more visualization of endocardium when compared with the combination of fundamental imaging and contrast (4.8 + or - 0.5 versus 4.1 + or - 1.0, P <.001). In addition, interobserver agreement for border detection increased from 83% in fundamental mode without contrast to 95% with the use of NTHI with Optison (P <.001). CONCLUSION: As defined in 200 cases, the combination of NTHI with Optison contrast results in nearly complete and consistent endocardial border definition.

Perception of mistuned harmonics in complex sounds by the bullfrog (Rana catesbeiana).

The ability of 73 male bullfrogs (Rana catesbeiana) to detect single mistuned harmonics in an otherwise periodic signal was studied. Bullfrogs in their natural environment were presented with playbacks of synthetic signals, resembling their species advertisement calls, that differed in the frequency of 1 harmonic component (out of 22). There were significant differences in the number and latency of the males' evoked vocal responses to these stimuli, suggesting that males were sensitive to the differences between the sounds. Differences in envelope shape (rate and depth of amplitude modulation) produced by the harmonic mistunings may underlie the differences in response. Frogs, like birds and humans, can discriminate sounds on the basis of harmonic structure, indicating that this is a general perceptual trait shared among vertebrates.

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors.

BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.

Metabolism of carvedilol in dogs, rats, and mice.

The excretion and biotransformation of carvedilol [1-[carbazolyl-(4)-oxy]-3-[(2-methoxyphenoxyethyl)amino]-2-p ropanol], a new, multiple-action, neurohormonal antagonist that exhibits the combined pharmacological activities of beta-adrenoreceptor antagonism, vasodilation, and antioxidation, were investigated in dogs, rats, and mice. Carvedilol was absorbed well, and biliary secretion was predominant in each species. Carvedilol was metabolized extensively in each species, and elimination of unchanged compound was minor in bile duct-catheterized rats and dogs. In dogs, glucuronidation of the parent compound and hydroxylation of the carbazolyl ring, with subsequent glucuronidation, were the major metabolic pathways. Rats showed the simplest metabolite profile; the primary metabolites were formed by hydroxylation of the carbazolyl ring, with subsequent glucuronidation. Mice displayed the most complicated metabolite profile; glucuronidation of the parent compound and hydroxylation of either the carbazolyl or phenyl ring, with subsequent glucuronidation, were the major metabolic routes. O-Dealkylation was a minor pathway in all species examined.

Microchimerism and HLA-compatible relationships of pregnancy in scleroderma.

BACKGROUND: Fetal cells can be found in the maternal circulation in most pregnancies. Fetal progenitor cells have been found to persist in the circulation of women many years after childbirth. We tested the hypothesis that microchimerism is involved in the pathogenesis of scleroderma. Scleroderma is of interest because of a strong female predilection, an increased incidence in the years after childbearing, and clinical similarities between scleroderma and chronic graft-versus-host disease after allogeneic bone-marrow transplantation. We also investigated whether HLA-compatibility of a child was associated with later development of scleroderma in the mother. METHODS: We enrolled 40 women who had previously given birth to at least one son--16 healthy controls, 17 scleroderma patients, and seven healthy sisters of patients. We used quantitative PCR to amplify a Y-chromosome-specific sequence in whole peripheral blood from these women. Also 32 controls with 58 children, and 21 scleroderma patients with 47 children were HLA genotyped. FINDINGS: The mean number of male cell DNA equivalents among controls was 0.38 cells per 16 mL whole blood (median 0 [range 0-2]) and 11.1 (6.0 [0-61]) among scleroderma patients (p = 0.0007). Controls' youngest sons were born a mean of 15.4 years previously, and scleroderma patients' sons 18.5 years previously. Some scleroderma patients had concentrations of male DNA higher than those found in most pregnant women. HLA-class II compatibility of a child from the mother's perspective was more common among scleroderma patients than among controls, but was not essential for persistence of male DNA in maternal peripheral blood. INTERPRETATION: Low concentrations of male DNA can be detected in healthy women decades after the birth of a son. Microchimerism in scleroderma patients could be secondary to the underlying disease. However, the finding that HLA class II compatibility of a child was more common for scleroderma patients than for controls, supports the possibility that microchimerism may be involved in the pathogenesis of scleroderma.