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Background The survival after lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension has been reportedly the lowest among the major diagnostic categories of lung transplant recipients. Methods Retrospective analysis was performed for lung and heart-lung transplant recipients for idiopathic pulmonary arterial hypertension from 1982 to 2006. The patients were divided into 2 groups, based on the era; group 1: 1982 to 1993, and group 2: 1994 to 2006. Since 1994, we have introduced our current protocols including prostaglandin E 1 and nitroglycerin for donor lung preservation, and lung protection with cold and terminal warm blood pneumoplegia as well as immunosuppression with alemtuzumab induction. These modifications were introduced in different years over a wide span of time (1994 to 2003). Results Group 1 had 59 patients (35 ± 1 years old, ranging 15 to 53, 20 male and 39 female) with 7 single lung, 11 double lung, and 41 heart-lung, whereas group 2 had 30 (43 ± 2 years old, ranging 17 to 65, 9 male and 21 female) with 2 single, 20 double, and 8 heart-lung transplantations. The recipient age was significantly ( p = 0.004) higher in group 2, and group 2 had significantly older (35 ± 3 vs 26 ± 1, p = 0.002) and more female donors (73% vs 41%, p = 0.007) compared with group 1. The actuarial survival was significantly ( p = 0.004) better in group 2 with 86% at 1 year, 75% at 5 years, and 66% at 10 years compared with group 1 with 58% at 1 year, 39% at 5 years, and 27% at 10 years. Conclusions With our current pulmonary protection and immunosuppression, the long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension is excellent.

An array of Neutral-Current Detectors (NCDs) has been built in order to make a unique measurement of the total active flux of solar neutrinos in the Sudbury Neutrino Observatory (SNO). Data in the third phase of the SNO experiment were collected between November 2004 and November 2006, after the NCD array was added to improve the neutral-current sensitivity of the SNO detector. This array consisted of 36 strings of proportional counters filled with a mixture of $^3$He and CF$_4$ gas capable of detecting the neutrons liberated by the neutrino-deuteron neutral current reaction in the D$_2$O, and four strings filled with a mixture of $^4$He and CF$_4$ gas for background measurements. The proportional counter diameter is 5 cm. The total deployed array length was 398 m. The SNO NCD array is the lowest-radioactivity large array of proportional counters ever produced. This article describes the design, construction, deployment, and characterization of the NCD array, discusses the electronics and data acquisition system, and considers event signatures and backgrounds., 32 pages, 18 figures, 6 tables

This article provides the complete description of resultsfrom the Phase I data set of the Sudbury Neutrino Observatory (SNO). ThePhase I data set is based on a 0.65 kt-year exposure of heavy water tothe solar 8B neutrino flux. Included here are details of the SNO physicsand detector model, evaluations of systematic uncertainties, andestimates of backgrounds. Also discussed are SNO's approach tostatistical extraction of the signals from the three neutrino reactions(charged current, neutral current, and elastic scattering) and theresults of a search for a day-night asymmetry in the ?e flux. Under theassumption that the 8B spectrum is undistorted, the measurements fromthis phase yield a solar ?e flux of ?(?e) =1.76+0.05?0.05(stat.)+0.09?0.09 (syst.) x 106 cm?2 s?1, and a non-?ecomponent ?(? mu) = 3.41+0.45?0.45(stat.)+0.48?0.45 (syst.) x 106 cm?2s?1. The sum of these components provides a total flux in excellentagreement with the predictions of Standard Solar Models. The day-nightasymmetry in the ?e flux is found to be Ae = 7.0 +- 4.9 (stat.)+1.3?1.2percent (sys.), when the asymmetry in the total flux is constrained to bezero.

The organ transplantation process involves a series of events and time periods, from the initial transplant evaluation through the extended years after surgery. Each event and time period is associated with multiple health-related and psychosocial stressors. Identification of key stressors will allow for the development of interventions to reduce their negative effects on patients' health and well-being.

Characterization and Impact of Pulmonary Hypertension on Outcomes After Left Ventricular Assist Device Implantation V.N. Selby ,1 J.J. Teuteberg,2 I.E. Allen,3 R.J. Tedford,4 R.L. Kormos,5 T. De Marco.1 1Division of Cardiology, University of California, San Francisco, San Francisco, CA; 2Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA; 3Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA; 4Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD; 5Department of Surgery, University of Pittsburgh, Pittsburgh, PA.

The Thoratec Implantable Ventricular Assist Device (Thoratec Corporation, Pleasanton, Calif) can be used for univentricular or biventricular support in patients with a body surface area as low as 1.3 m(2). Results of the multicenter clinical trial are reviewed.Between October 2001 and June 2004, a total of 39 patients at 12 institutions were supported with the Thoratec Implantable Ventricular Assist Device. Twenty-four patients (62%) received left ventricular assist devices and 15 (38%) received biventricular assist devices. Indications included bridge to transplantation (n = 30) and postcardiotomy failure (n = 9). The control group included 100 patients from the Food and Drug Administration approval submissions for the paracorporeal version of the ventricular assist device.Twenty-eight male and 11 female patients, with mean age of 48 years (16-71 years) and body surface area of 1.9 m(2) (1.3-2.4 m2) were supported for 3938 patient-days (10.8 patient-years). Mean left ventricular assist device flow index on the first postoperative day was 2.5 +/- 0.5 L/(min x m2). Mean duration of support was 101 days (9-597 days). Eighteen patients were discharged after a mean duration of 96 days. There were no ventricular assist device failures. Complications included 13 cases of bleeding requiring reexploration (33.3%), 1 embolic and 2 hemorrhagic strokes (7.7%), 5 driveline infections (12.8%), and 2 pocket infections (5%). Support to successful outcomes was 70% for bridge to transplantation and 67% for postcardiotomy recovery, versus historical results for the paracorporeal ventricular assist device of 69% for bridge to transplantation and 48% for postcardiotomy recovery.The Thoratec Implantable Ventricular Assist Device is a new implantable pulsatile ventricular assist device that allows hospital discharge for patients as a bridge to transplantation or for postcardiotomy failure. It is the first Food and Drug Administration-approved implantable ventricular assist device with biventricular capability.

Survival and functional outcomes for lung transplant recipients continue to lag behind those for heart recipients. Whether these poorer physical outcomes translate into poorer quality of life (QOL) for lung recipients relative to heart recipients is unknown. Lung versus heart transplant recipients' perceptions of QOL were longitudinally compared at three time-points across the first year posttransplant. Additionally, potentially important predictors of patient QOL were examined. Adult transplant recipients (N = 199) participated in semi-structured interviews that included measures of QOL, optimism, mastery, social support, religiosity and coping. Temporal patterns of QOL change were compared between lung and heart recipients who survived until 1 year posttransplant using mixed-model, hierarchical analysis of variance (ANOVA). Demographic and psychosocial predictors were examined with multiple regression analysis to identify the unique effects of each variable on QOL 1 year posttransplant. While heart recipients' QOL across several domains was higher shortly after transplant, lung patients' QOL improved and was equivalent to that of heart recipients by 1 year posttransplant. Greater optimism and support from friends predicted better QOL in physical, psychological and social domains. Conversely, avoidant coping strategies predicted poorer physical functioning. Thus, while clinical interventions designed to improve QOL posttransplant should be tailored to transplant recipients' initial psychosocial assets and liabilities, they need not be distinguished by transplant type.

Left ventricular assist devices (LVADs) have been used effectively as a "bridge" to cardiac transplantation and as destination therapy in patients with advanced heart failure. Ventricular arrhythmias (VAs) have been reported to occur in LVAD-supported patients, although their incidence, risk factors, and clinical significance have not been characterized. In this study, 111 patients who received LVAD support as a bridge to cardiac transplantation at the University of Pittsburgh Medical Center from January 1987 to June 2001 were evaluated. Clinically significant VA was defined as ventricular fibrillation, sustained ventricular tachycardia, or nonsustained ventricular tachycardia with symptoms requiring antiarrhythmic therapy. Patients were grouped on the basis of the presence or absence of VAs. VAs occurred in 24 patients (22%) during device support. Ischemic heart disease was the cause of heart failure in 71% of patients (17 of 24) in the VA group and 45% of patients (39 of 87) in the group without VAs (p0.05). The mortality rate was significantly higher (p0.001) during LVAD support in the group with VAs (33%) compared with the group without VAs (18%). In the group with VAs, the early (or=1 week) occurrence of VAs was associated with a significantly higher (p0.001) mortality rate (54%) compared with late (1 week) occurrence (9%). In conclusion, although clinically significant VAs occur in patients with heart failure receiving LVAD support, the overall incidence is low. VAs are more frequent in patients with ischemic heart failure, and their occurrence is associated with greater mortality. The occurrence of VAs early after LVAD implantation, in particular, predicts a higher mortality rate.

Hybrid density functional calculations with effective core potential basis sets are performed for monomeric group 13/15 and group 14/14 analogues of cyclohexane, as well as for three different pseudo-two-dimensional structures that can be formed from expanding one and two concentric rings around the central one (trans-fused chairs, a rolling combination of trans- and cis-fused chairs, and cis-fused boats). Varying contributions from torsional strain, angle strain, electrostatics, and nontraditional H-H hydrogen bonding lead to different orderings and magnitudes of motif energies in the various systems: Homoatomic SiSi and GeGe systems prefer the trans-fused chair alternative and heteroatomic systems GaN, SiC, and GeC prefer the rolling chair. Decomposition of structure energies into characteristic fragment contributions indicates that pseudo-one-dimensional rods of poly(imidogallane) are thermodynamically more stable than any of the pseudo-two-dimensional structures.

A search has been made for neutrinos from the hep reaction in the Sun and from the diffuse supernova neutrino background (DSNB) using data collected during the first operational phase of the Sudbury Neutrino Observatory, with an exposure of 0.65 kilotonne-years. For the hep neutrino search, two events are observed in the effective electron energy range of 14.3 MeV, Comment: 12 pages, 5 figures, accepted for publication by ApJ. Minor updates to address referees comments

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Results are reported from the complete salt phase of the Sudbury Neutrino Observatory experiment in which NaCl was dissolved in the {sup 2}H{sub 2}O (''D{sub 2}O'') target. The addition of salt enhanced the signal from neutron capture as compared to the pure D{sub 2}O detector. By making a statistical separation of charged-current events from other types based on event-isotropy criteria, the effective electron recoil energy spectrum has been extracted. In units of 10{sup 6}cm{sup -2}s{sup -1}, the total flux of active-flavor neutrinos from {sup 8}B decay in the Sun is found to be 4.94{sub -0.21}{sup +0.21}(stat){sub -0.34}{sup +0.38}(syst) and the integral flux of electron neutrinos for an undistorted {sup 8}B spectrum is 1.68{sub -0.06}{sup +0.06}(stat){sub -0.09}{sup +0.08}(syst); the signal from ({nu}{sub x},e) elastic scattering is equivalent to an electron-neutrino flux of 2.35{sub -0.22}{sup +0.22}(stat){sub -0.15}{sup +0.15}(syst). These results are consistent with those expected for neutrino oscillations with the so-called large mixing angle parameters and also with an undistorted spectrum. A search for matter-enhancement effects in the Earth through a possible day-night asymmetry in the charged-current integral rate is consistent with no asymmetry. Including results from other experiments, the best-fit values for two-neutrino mixing parameters are {delta}m{sup 2}=(8.0{sub -0.4}{sup +0.6})x10{sup -5}more » eV{sup 2} and {theta}=33.9{sub -2.2}{sup +2.4} degrees.« less

The RNA recognition motif (RRM) is one of the most common RNA binding domains. We have investigated the contribution of three highly conserved aromatic amino acids to RNA binding by the N-terminal RRM of the U1A protein. Recently, we synthesized a modified base (A-4CPh) in which a phenyl group is tethered to adenine using a linker of 4 methylene groups. The substitution of this base for adenine in the target RNA selectively stabilizes the complex formed with a U1A protein in which one of the conserved aromatic amino acids is replaced with Ala (Phe56Ala). In this article, we report molecular dynamics (MD) simulations that probe the structural consequences of the substitution of A-4CPh for adenine in the wild type and Phe56Ala U1A–RNA complexes and in the free RNA. The simulations suggest that A-4CPh stabilizes the complex formed with Phe56Ala by adopting a folded conformation in which the tethered phenyl group fills the site occupied by the phenyl group of Phe56 in the wild-type complex. In contrast, an extended conformation of A-4CPh is predicted to be most stable in the complex formed with the wild-type protein. The calculations indicate A-4CPh is in an extended conformation in the free RNA. Therefore, preorganizing the structure of the phenyl-tethered base for binding may improve both the affinity and specificity of the RNA containing A-4CPh for the Phe56Ala U1A protein. Taken together, the previous experimental work and the calculations reported here suggest a general design strategy for altering RRM–RNA complex stability. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 256–269, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

A search has been made for sinusoidal periodic variations in the 8B solar neutrino flux using data collected by the Sudbury Neutrino Observatory over a 4-year time interval. The variation at a period of 1 yr is consistent with modulation of the 8B neutrino flux by the Earth's orbital eccentricity. No significant sinusoidal periodicities are found with periods between 1 d and 10 years with either an unbinned maximum likelihood analysis or a Lomb-Scargle periodogram analysis. The data are inconsistent with the hypothesis that the results of the recent analysis by Sturrock et al., based on elastic scattering events in Super-Kamiokande, can be attributed to a 7% sinusoidal modulation of the total 8B neutrino flux.

A recent study has shown that left ventricular (LV) end-systolic elastance (E,) , a load independent parameter of contractility, could be estimated from a single ejecting beat by estimating peak isovolumic pressure (IP ). The purpose of this study was to appyy this method to the human right ventricle. In patients undergoing left ventricular assist device (LVAD) implantation, these estimated values were compared to results obtained from preload altering by vena cava occlusion. The correlation coefficient between estimated and experimentally measured IP was 0.85. Estimated E, approximateTexperimenta1 E,, in six 08 nine experiments.

Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients.We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months.By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy.Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.

Purpose Previous studies suggest infection may confer risk for thrombotic complications (TC) after LVAD. We hypothesized that in discharged (disch) LVAD patients (pts), there is an increased rate of TC within 6 weeks (wks) after a major infection. Methods and Materials We reviewed INTERMACS (4/2008 to 6/2012) to identify disch pts with continuous flow LVAD, with ≥1 infection after disch. INTERMACS definitions were used. Infection was categorized as: 1) pump infection (pump); 2) percutaneous site/pocket infection (device related); 3) sepsis; and, 4) localized non-device infection (non-device). TC were: 1) neurological dysfunction; 2) pump thrombosis; 3) arterial non-central nervous system and, 4) hemolysis (plasma free hemoglobin >40 mg/L). TC rates (TC per 100 mo of pt exposure) 6 wks pre-infection were compared to rates 6 wks post-infection. P-values were calculated with McNemar’s test. Results Of 4124 disch LVAD pts, 1253 (30%) had a major infection post-disch (pump, n=5; device related, n=517; sepsis, n=203; non-device, n=528). Key features of infected pts (mean±SD and %) were: age (54.6±8.3 yrs.), male (75.4%), diabetes (43.8%), destination therapy (27.9%). Last INR prior to TC was 2.1±1.3. There was no significant difference in TC rate after an infection vs pre-infection (6.63 vs 6.27; p=0.67). When analyzed by category of infection, there was a higher rate of TC after device related infection. Conclusions In disch LVAD pts there was a significantly higher rate of TC driven by neurological dysfunction and pump thrombosis within 6 wks of a device related infection. There was no significant association between other infections and TC. This data suggests increased risk of TC following device related infection. Percutaneous Site/Pocket Infection Pre-infection (n; rate) Post-infection (n; rate) p-value Total TC 12; 1.8 33; 4.9 0.005 Neurological dysfunction 6; 0.9 18; 2.7 0.01 Pump thrombosis 2; 0.3 7; 1.0 0.06 Non-CNS TC 0; 0.0 1; 0.2 -- Hemolysis 4; 0.6 7; 1.04 0.48

Purpose Post-operative right ventricular failure (RVF) is a major source of morbidity and mortality in left-ventricular assist device (LVAD) recipients. Predicting and defining RVF is challenging. Methods and Materials Prospectively collected pre-op echo and hemodynamic data of LVAD recipients were analyzed including RV mid free wall longitudinal myocardial strain (LMS) by speckle tracking. Four definitions of RVF were used: 1) permanent right ventricular assist device (pRVAD), 2) pRVAD or temporary RVAD (any RVAD), 3) any RVAD or 14 days of post-op inotropic therapy (14d), or 4) any RVAD or 7 days of post-op inotropic therapy (7d). Results Of the 41 pts, 8 (20%) had RVF defined by pRVAD, 14 (34%) by any RVAD, 19 (46%) by 14d, and 32 (78%) by 7d. RVF was associated with lower LMS and cardiac index (CI) and higher right atrial pressure (RAP) in all outcome groups except 7d (table). ROC analysis yielded increasing LMS cutoffs for RVF defined by pRVAD (LMS −9.7%: sensitivity/specificity 75%/85%), any RVAD (LMS −11.4%: 71%/70%), and 14d (−13.2%: 79%/50%). By multivariate analysis, LMS independently predicted RVF defined by pRVAD (HR 1.41, p=0.02), any RVAD (HR 1.28, p=0.03), or 14d (HR 1.24, p=0.04). Conclusions The incidence of RVF differs considerably depending on the definition. Among echo and hemodynamic data, LMS seems most useful to predict RVF in LVAD candidates for most definitions, with progressive cutoffs for more severe RVF. Outcome LMS (%) TAPSE (cm) RV FAC (%) RAP (mm Hg) CI (L/min/m2) pRVAD -7.3±4.1 vs -12.9±4.3 p=0.005 1.5±0.4 vs 1.7±0.4 p=0.4 19±8 vs 24±10 p=0.3 20±12 vs 12±5 p=0.049 1.6±0.5 vs 2.1±0.6 p=0.03 Any RVAD -8.9±4.4 vs -13.4±4.3 p=0.006 1.5±0.5 vs 1.7±0.4 p=0.3 21±8 vs 24±11 p=0.5 18±9 vs 12±5 p=0.03 1.8±0.4 vs 2.2±0.6 p=0.04 14d -10.0±4.8 vs -13.4±4.2 p=0.02 1.5±0.4 vs 1.7±0.4 p=0.1 23±9 vs 23±11 p=0.9 16±9 vs 11±5 p=0.06 1.8±0.5 vs 2.2±0.6 p=0.03 7d -11.0±1.8 vs -14.8±5.4 p=0.14 1.6±0.1 vs 1.8±0.1 p=0.3 22±9 vs 25±12 p=0.6 14±8 vs 11±5 p=0.3 2.0±0.6 vs 2.1±0.4 p=0.7 (+) Outcome vs (-) Outcome

Purpose INTERMACS data show that select AE’s lead to higher mortality during VAD support. However, the extent to which these AE’s experienced early (within 60 days) after VAD implant effect long-term survival after this time period is not known for those with a CF-VAD. Methods and Materials We analyzed prospectively collected data from a single-center database on adults implanted with a CF-VAD (2004-2011) who survived beyond 60 days. 14 different classes of AE’s as defined by INTERMACS were assessed during the first 60 days post-implant. For each AE, 1-year survival was compared for those with and without the AE using Kaplan-Meier analysis. Any class of AEs at least marginally associated (p Results In 91 patients, the mean age was 56 years, 81% were male, 82% were white, and 65% were bridge to transplant. The occurrence of right ventricular failure (RVF), renal, neurologic, and respiratory events in the first 60 days of support were associated with significantly increased mortality at 12 months (p figure 1 ] Conclusions Of the 14 major AE’s experienced early after CF-VAD implantation, only RVF, renal, neurologic, and respiratory events had significant long-term effects on mortality that persisted beyond the initial event. The only early AE that was an independent predictor of poor late outcome was RVF.

Purpose Patients with continuous flow left ventricular assist devices (CF-LVAD) require chronic anticoagulation with warfarin. The time in therapeutic range for a physician-based (MD) versus management by an anticoagulation clinic (AC) has not been well described. Methods and Materials All INRs and bleeding/thrombotic complications for patients with CF-LVAD from 1/1/12 to 11/15/12 at a single center were reviewed. Management of anticoagulation was changed from MD to AC clinic on 7/1/12. Time in therapeutic range (TTR) was determined using the fraction of INRs in range; values during hospitalization were excluded from analysis. Goal INR: HeartMate II (HMII) 1.5-3, HeartWare (HW) 2.5-3.5. Results There were a total of 48 patients who were on support during the period studied, with 1095 INR values evaluated; mean age 48, 48% ischemic, 90% male, 60% DT, 73% HeartMateII, 27% HeartWare. There were no differences in TTR between MD and AC, overall or by device. The HW group had a significantly lower TTR (52.5% v. 71%, p figure 1 ] Conclusions There was no difference in the TTR for patients with CF-LVAD between physician and anticoagulation clinic management, with about a third of patients overall not at goal. When not at goal about half of the patients were subtherapeutic, with HW patients more likely to be subtherapeutic than HMII. Strategies to maximize TTR for patients with CF-LVAD are needed.

A rotary blood pump inherently provides only one noninvasive "observable'" parameter (motor current) and allows for only one "controllable" parameter (pump speed). To maintain the systemic circulation properly, the pump speed must be controlled to sustain appropriate outlet Hows and perfusion pressure while preventing pulmonary damage caused by extremes in preload. Steady-state data were collected at repeated intervals during chronic trials of the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, California, U.S.A.) in sheep (n = 7) and calves (n = 12). For each data set, the pump speed was increased at increments of 500 rpm until left ventricular and left atrial emptying was observed by left atrial pressure diminishing to zero. The effect of decreasing preload was evaluated perioperatively by inferior vena cava occlusion at a constant pump speed. Fourier analysis established a relationship between changes in the pump preload and the power spectra of the pump current waveform. Based on these results, a control method was devised to avoid ventricular collapse and maintain the preload within a physiologic range. The objective of this controller is the minimization of the second and third harmonic of the periodic current waveform. This method is intended to provide a noninvasive regulation of the pump by eliminating the need for extraneous transducers.

Background. There is interest in expanding ventricular assist device use from short-term bridging to transplantation to long-term and permanent support. Methods. We have reviewed the outcome of 162 patients who had a mechanical bridge to transplantation that lasted at least 60 days. Eighty-five patients received the HeartMate, 40 the Novacor, and 37 the Thoratec device. Results. Of the 162 patients, 125 received transplants, and 115 survived after transplantation (93%). Within the group there were 174 complications including 54 infections of the driveline, 73 other infections, and thromboembolic strokes in 47. Infections of the driveline were considered major in 24 of 54 cases, and other infections were major in 36 of 73 cases. Twenty-seven of those who sustained thromboembotic events had residual effects. Of 11 patients with a major stroke and infection, only 1 survived transplantation. Eighty-two patients were supported between 60 and 100 days, 63 patients between 101 and 200 days, 12 patients between 201 and 300 days, and only 5 patients in excess of 300 days. A greater percentage of candidates died waiting between 101 and 200 days than between 60 and 100 days (25% versus 10%). The incidence of complications also rose in those patients bridged more than 100 days. Conclusions. The data reinforce the excellent results obtained in the bridge to transplantation trials that reported a shorter duration of support. For those interested in extended bridge to transplantation or permanent use of the currently available devices, the results suggest reasonable success can be anticipated, but the serious infections and strokes tend to be more common with longer duration of support.

Upper limits on the \nuebar flux at the Sudbury Neutrino Observatory have been set based on the \nuebar charged-current reaction on deuterium. The reaction produces a positron and two neutrons in coincidence. This distinctive signature allows a search with very low background for \nuebar's from the Sun and other potential sources. Both differential and integral limits on the \nuebar flux have been placed in the energy range from 4 -- 14.8 MeV. For an energy-independent ��_e --> \nuebar conversion mechanism, the integral limit on the flux of solar \nuebar's in the energy range from 4 -- 14.8 MeV is found to be ��_\nuebar, submitted to Phys. Rev. D

Background. Family members adopt key caregiving roles in the maintenance of transplant recipients' health. While the bulk of the caregiving literature suggests that rates of psychiatric disorder should be high in these caregivers, the potential benefits of transplantation may instead lead to less distress than in other caregiving situations. We examined prevalence and risk factors for depressive and anxiety-related disorders in caregivers throughout 3 years after their family member's heart transplant.Method. A total of 190 caregivers (97% of eligible respondents) were enrolled. They received psychiatric and psychosocial evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis determined cumulative rates of psychiatric disorders and the impact of potential risk factors.Results. Rates of depressive and anxiety-related disorders met or exceeded other caregiver populations' rates. By 3 years post-transplant, cumulative onset rates were: Major Depressive Disorder (MDD), 31·6%, Adjustment disorders, 35·4% (29·4% with anxious mood); Post-Traumatic Stress Disorder related to the transplant (PTSD-T), 22·5%, Generalized Anxiety Disorder, 7·3%, and any assessed disorder, 56·3%. PTSD-T occurred primarily during the first year post-transplant. Other disorders' rates increased over the entire study period. Risk for disorder was elevated by positive lifetime history of psychiatric disorder, greater post-transplant caregiving responsibilities, and a poorer relationship with the patient. Risk for MDD was further increased by caregiver unemployment, and risk for anxiety disorders was further increased by younger age, low sense of personal mastery, and high use of avoidance coping strategies.Conclusions. Transplantation is associated with costs and benefits for not only patients but family caregivers. Caregivers' risk for psychiatric illness should be considered when developing interventions to promote families' long-term adjustment to the transplant process.

Although quality of life (QOL) is generally improved by heart transplantation, medical noncompliance and mental health and QOL limitations often emerge and persist. Transplant teams' ability to address these issues is hampered because many patients reside long distances from the transplant program. We therefore conducted the first empirical evaluation of an internet-based psychosocial intervention for heart recipients and their families.Based on focus group work and previous research, a multifaceted web-based intervention was developed with stress and medical regimen management workshops; monitored discussion groups; access to electronic communication with the transplant team; and information on transplant-related health issues. Intervention effectiveness was evaluated with 20 patients and family caregivers who used the website for 4 months (plus usual clinical care). Pre- and post-intervention assessments of mental health, QOL and medical compliance were performed. Comparison groups of 40 patients and their caregivers who received only usual care were similarly assessed.Relative to the comparison groups, intervention patients' depressive and anxiety symptoms, and caregivers' anxiety and hostility symptoms declined significantly (P0.05). QOL in social functioning significantly improved. Mental health and QOL benefits were greater among more frequent users of the website. Overall, intervention patients' medical compliance did not change. However, the sub-group using the website's medical regimen workshop showed significantly better compliance at follow-up than all other patients in attending clinic appointments, completing blood work and following diet.These preliminary findings suggest that a web-based intervention could have a vital role in follow-up care and in patients' and families' adjustment to heart transplantation.

Background A polymorphism exists in the tumor necrosis factor α (TNF-α) promoter (position −308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-α production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients. Methods We prospectively analyzed 57 subjects (aged 54 ± 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 ± 605 days) and the frequency of allograft rejection (biopsy Grade ≥2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups. Results The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 ± 11 days; Group B, 20 ± 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35). Conclusion The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.

We present the first exptl. results based on the jet boost algorithm, a technique to select unbiased samples of gluon jets in e+e- annihilations, i.e. gluon jets free of biases introduced by event selection or jet finding criteria. Our results are derived from hadronic Z0 decays obsd. with the OPAL detector at the LEP e+e- collider at CERN. First, we test the boost algorithm through studies with HERWIG Monte Carlo events and find that it provides accurate measurements of the charged particle multiplicity distributions of unbiased gluon jets for jet energies larger than about 5 GeV, and of the jet particle energy spectra (fragmentation functions) for jet energies larger than about 14 GeV. Second, we apply the boost algorithm to our data to derive unbiased measurements of the gluon jet multiplicity distribution for energies between about 5 and 18 GeV, and of the gluon jet fragmentation function at 14 and 18 GeV. In conjunction with our earlier results at 40 GeV, we then test QCD calcns. for the energy evolution of the distributions, specifically the mean and first two nontrivial normalized factorial moments of the multiplicity distribution, and the fragmentation function. The theor. results are in global agreement with the data, although the factorial moments are not well described for jet energies below about 14 GeV. [on SciFinder (R)]

Objectives: Continuous flow left ventricular assist systems (LVAS) are being discussed as a destination therapy. LVAS patients will have expanded activity of daily life, including exercise. In this study, we analyzed the effects of exercise on blood flow in the distal thoracic aorta of LVAD implanted animals. Methods: Five calves with a continuous flow LVAS exercised on treadmill at two different pump flow rates (PFR), 60 ‐ 80% (high PFR) and 25 ‐ 30% (low PFR) of pulmonary artery flow rate. Pump, pulmonary artery and descending thoracic aorta flow waves were recorded before, during and after exercise. Systolic and diastolic flow volume in each cardiac cycle in pump and descending thoracic aorta flow was calculated. Results: (1) Average flow rates ‐ Pulmonary artery and descending thoracic aorta flow rates increased with heart rate during exercise and there was no difference between groups. (2) Pump flow wave ‐ Pump regurgitation increased temporally during exercise at both PFRs, but sustained incidences of regurgitation after exercise were only observed at low PFR. Systolic and diastolic pump flow volume decreased during exercise at both PFRs, but systolic volume increased and diastolic volume decreased significantly after exercise at low PFR. (3) Descending thoracic aorta flow wave ‐ At high PFR, systolic volume of descending thoracic aorta increased but diastolic flow volume decreased during exercise. At low PFR, both systolic and diastolic volume of the descending thoracic aorta decreased during exercise, but systolic volume increased and diastolic volume decreased after exercise. Systolic volume of the descending thoracic aorta in low PFR was significantly greater and diastolic volume was less than those in high PFR during and after exercise. Conclusion: Exercise temporarily increases pump regurgitation with continuous flow LVAS support. Average flow rate of the descending thoracic aorta was maintained by compensation from increased heart rate, although the diastolic flow of the descending thoracic aorta decreased after exercise at the lower pump flow rate. Further study will be needed to evaluate whether or not this flow decrease causes hemodynamic and/or an oxygen delivery mismatch to peripheral tissue. q 2003 Elsevier B.V. All rights reserved.

Background Many lung and heart–lung transplant recipients experience distressing physical symptoms and elevated physical impairment levels. Although post-transplant complications and secondary illnesses may largely account for these health limitations, patients’ psychosocial well-being may influence them as well. We examined the contribution of psychosocial variables to patients’ experience of physical symptoms and physical impairment. Methods The study consisted of a cross-sectional sample of 50 patients (36 lung, 14 heart–lung) at between 2 and 17 months post-transplant. They were interviewed to assess physical symptoms, current physical impairment and psychosocial well-being in the areas of mental health, sense of mastery and coping. Medical record reviews established the presence of medical complications and secondary illnesses concurrent with the interviews. Descriptive analyses examined the range of symptoms and levels of physical impairment experienced. Bivariate analyses and multivariate linear regression examined relationships between key variables. Results Average number of physical symptoms and level of physical impairment met or exceeded levels reported in other transplant samples. Elevated depressive and anxiety symptoms, a low sense of mastery, and the presence of concurrent medical complications were each associated with increased number of physical symptoms and physical impairment level. When the impact of concurrent medical complications was controlled, recipients with elevated psychologic distress remained significantly more likely to report more physical symptoms and higher physical impairment levels. Conclusions Patients’ physical health status may be influenced by many factors. To the extent that psychologic distress increases the likelihood of perceived physical limitations, timely identification and treatment of distress may help to maximize quality of life after lung and heart–lung transplantation.

Over the last 2 decades, mechanical circulatory support devices have been developed with the goal of supporting patients with advanced heart failure as a bridge to cardiac transplantation, a bridge to recovery, and an alternative to transplantation (also called chronic or destination therapy). The current generation of devices provides a differentiated spectrum of circulatory support. The major limitations of mechanical circulatory support devices are infection, coagulopathies and device dysfunction. The Scientific Council on Mechanical Circulatory Support of the International Society for Heart and Lung Transplantation has established an international database to generate critical data to advance knowledge about the effectiveness of mechanical circulatory support device therapy for one of the most difficult and costly contemporary medical problems, the malignant syndrome of advanced heart failure.

Summary form only given. The emergence of artificial organ (AO) technologies as a conventional therapy for end stage failure and alternative to organ replacement has produced a need for dedicated clinical personnel to manage patients supported by them. These focused individuals provide clinical, educational and technical support in the hospital surroundings, and because a principal goal of AO device application is to enhance quality of life, they also serve as a resource for patients living outside the hospital or at home. Furthermore, AO specialists furnish post-marketing feedback to manufacturers and clinicians yielding superior products that should enhance patient outcomes. Currently, more than 1000 patients receive mechanical cardiac support (MCS) devices each year. Recent estimates indicate that this number could surpass 20,000 within in the next five years. With the impending manifestation of other AO technologies, e.g., the bio-artificial liver and chronic artificial lung, many thousands of patients and several clinical sites worldwide can be expected to utilize sophisticated mechanical devices. To accommodate the widespread application of AO technologies, new "best practice" models for patient care, training, and follow up will need to be fashioned and refined. In addition, clinical centers may be required to have experts on site to supervise the utilization of AO devices. We propose an innovative model support system that utilizes professional biomedical engineers, with both clinical and technical expertise, to interface with these technologies, in the structure of a service-based company. Our center has developed such a model program in which a cadre of biomedical engineers undertakes both AO technical support and patient care responsibilities. This group has participated in the support and care of more than 220 MCS patients over a 15-year period; of the MCS patients, more than 50 have been managed following discharge home. In addition, the biomedical engineers have trained literally thousands of medical specialists to care for patients and AO systems in their own hospital and home settings. We believe that a biomedical engineering-based program model enhances the capacity of medical centers to utilize state-of-the art AO technologies, and could ultimately yield augmented AO devices and better outcomes for those patients who require these products.

Background: End-stage heart failure (HF) patients are at high risk of sudden cardiac death. This study evaluates the role of implantable cardiac defibrillators (ICDs) in HF patients awaiting cardiac transplantation. Methods: We identified 194 consecutive patients (age 51 ± 12 years) with New York Heart Association Class 3 or 4 HF (ejection fraction 22 ± 9%) listed for cardiac transplantation, 35 of whom underwent ICD implantation. Of the implanted patients, 16 (Group A) had an established indication for ICD implantation (cardiac arrest, n = 10; sustained ventricular tachycardia [VT], n = 3; and positive electrophysiology study, n = 3). Nineteen patients (Group B) underwent ICD implantation for non-established indications (syncope with non-ischemic cardiomyopathy, n = 4; non-sustained VT, n = 15). There were no procedural complications from ICD implantation. Results: During follow-up of 9.2 ± 10.1 months, there were 3 deaths in the ICD groups (A and B), and 40 in the control group (8.6% vs 25.2%, p = 0.032). Five patients in Group A and 6 in Group B (31%) received appropriate ICD therapy. The number of therapies per patient and the time to the first shock were similar between Groups A and B. Four of 6 Group B patients on outpatient inotropic therapy (67%) received appropriate ICD therapy. Conclusions: Selected end-stage heart failure patients awaiting heart transplantation, including those without established ICD indications, are at high risk for malignant arrhythmias and may benefit from ICD implantation. Patients with ICD seem to have improved survival compared to those without ICD. Randomized prospective studies are needed to confirm these findings.

The aim of this study was the evaluation of the thrombogenicity and the biocompatibility of the SunMedical EVAHEART left ventricular assist system (LVAS) coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer compared to a diamond-like carbon (DLC) coating. Four calves were implanted with the MPC polymer-coated LVAS. Eight calves were implanted with DLC coated LVAS. The thrombogenicity and biocompatibility of the pumps were evaluated. At explant, 60.0 +/- 37.2% (5-85%) of the pump surface area was still coated with MPC polymer after the duration of 45.0 +/- 32.0 days. In 1 out of 4 MPC and 2 out of 8 DLC coated pumps, there was a very small amount of thrombus around the seal ring; otherwise the blood contacting surfaces were free of thrombus. Major organs were normal except for a few lesions in kidneys from both groups. The MPC polymer coated EVAHEART LVAS seems to have low thrombogenicity and high biocompatibility similar to the DLC coated system. The current study demonstrated that the MPC polymer coating shows great promise for being used as an antithrombogenic substrate for the LVAS due to its ease of application, significant cost benefit, and reduction in anticoagulation therapy in acute postoperative period.

Background Peak exercise oxygen consumption is a widely used parameter to determine the need for transplant listing in patients with severe heart failure. Currently, β-blocker therapy is known to benefit patients with severe heart failure, although it has minimal or no effects on peak exercise oxygen consumption. This raises the hypothesis that peak exercise oxygen consumption transplant-listing criteria are not valid for patients with heart failure who receive β-blocker therapy. Methods We compared outcomes in patients with chronic heart failure who underwent heart transplant evaluation with peak exercise oxygen consumption ≤ 14.0 ml/kg/min and who were treated with β-blockers (n = 48) or who were not treated with β-blockers (n = 55). Results Outcomes were significantly better for patients treated with β-blockers (combined end-points of death, transplantation as United Network for Organ Sharing [UNOS] Status 1 or 2, and ventricular assist device placement, p = 0.0001). The 1-year survival was 92% and 3-year survival was 71% in the patients treated with β-blockers, and 69% and 48% in the patients not treated with β-blockers (compared with UNOS transplant survival data of 92% 1-year and 77% 3-year survival rates). Conclusions Patients with chronic heart failure and severe functional impairment who were treated with β-blockers have significantly better outcomes compared with similarly functionally impaired patients who were not treated with β-blockers, and these patients would not be expected to derive a survival benefit from transplantation. Thus, in patients treated with β-blockers, the use of peak exercise oxygen consumption as a criterion to list for heart transplantation may no longer be valid. Alternatively, non-usage of β-blockers may be a criterion to list for transplantation.

Hadronic Z0 decays with identified electrons or muons have been used to measure the forward-backward asymmetries of e^+e^- --> Z0 --> bbbar and e^+e^- --> Z0 --> ccbar events. The asymmetries at three centre-of-mass energies, and the average B mixing parameter, chi, are determined in a simultaneous fit to events with one or two lepton candidates., 23 pages, 3 figures, Submitted to Phys. Lett. B

The exclusive production of proton-antiproton pairs in the collisions of two quasi-real photons has been studied using data taken at rootS(ee) = 183 GeV and 189 GeV with the OPAL detector at LEP. Results are presented for p (p) over bar invariant masses, W, in the range 2.15 < W < 3.95 GeV. The cross-section measurements are compared with previous data and with recent analytic calculations based on the quark-diquark model.

The concept of mechanical circulatory assistance was established in the late 1950s and early 1960s with the first successful clinical use of the heart-lung machine for cardiopulmonary bypass. Attempts at developing total replacement artificial hearts and ventricular assist devices (VADs) were initiated in 1960s. The VADs, unlike total artificial hearts, which entirely replace the native heart, are mechanical pumps designed to augment the function of one or more chambers of the failing heart. A typical VAD is connected to the patient’s native circulation through a pair of tubes, one drawing blood from either the atrium or ventricle, and the other expelling blood into the arterial system. The VADs that are intended for long-term use are designed to be fully implanted in the body, with power transmitted across the skin. Devices intended for short-term use may reside outside the body, with blood traveling through tubes into the body.

A study of b quark hadronisation is presented using inclusively reconstructed B hadrons in about four million hadronic Z decays recorded in 1992-2000 with the OPAL detector at LEP. The data are compared to different theoretical models, and fragmentation function parameters of these models are fitted. The average scaled energy of weakly decaying B hadrons is determined to be =0.7193+-0.0016(stat)+0.0036-0.0031(syst), Comment: 26 pages, 8 figures