Increased operational costs of electricity generation in the Delaware River and Estuary from salinity increases due to sea-level rise and a deepened channel.

Like many estuaries in the world, salinity levels in the Delaware River and Estuary are expected to increase due to a deepened navigational channel and sea-level rise. This study estimated operational cost increases resulting from increased ambient salinity likely to be incurred at PSEG-Hope Creek, an evaporatively cooled electricity generating station. To estimate cost increases, a linked physical-economic model was developed to generate daily forecasts of salinity and the resulting changes in facility's cooling water treatment and pumping requirements. Salinity increases under potential future bathymetric configurations were simulated using a hydrodynamic model. On an equivalent annual basis (discounted at 5%), average cost increases were $0.4M per year, or approximately 0.1% of estimated total annual operating costs for the facility. Methods developed here could be employed at other facilities anticipating future salinity increases. Results inform cost-benefit analyses for dredging projects and contribute to estimates of the indirect costs to society from carbon emissions through sea-level rise. Future research refinements can focus on modeling changes in suspended sediment concentrations and estimating their impacts on operational costs.

Modeling the effect of water quality on the recreational shellfishing cultural ecosystem service of Buzzards Bay, Massachusetts.

Estuaries provide significant cultural ecosystem services, including recreation and tourism. Disruptions of estuarine biogeochemical processes resulting from environmental degradation could interrupt the flow of these services, reducing benefits and diminishing the welfare of local communities. This study focused on recreational shellfishing in Buzzards Bay, Massachusetts (41.55°N, 70.80°W). Relationships among measures of recreational shellfishing, estuarine water quality, and local socioeconomic conditions were tested to understand how the benefits of cultural ecosystem services to local communities might be affected by declining water quality. Transferring estimated economic benefits from an analysis of nearby municipalities, the study finds that increases in Chl a during the 24-year period were associated with losses in recreational shellfishing benefits of $0.08-0.67 million per decade. The approach presented here suggests a more broadly applicable framework for assessing the impacts of changes in coastal ecosystem water quality on the welfare of local communities.

Tissue T and B cell infiltration of primary and metastatic cancer.

Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer.

Exercise hemodynamics during long-term implantation of a left ventricular assist device in patients awaiting heart transplantation.

OBJECTIVES: The goal of this study was to assess patients with end-stage heart disease after implantation of a left ventricular assist device at rest and during exercise compatible with activities of daily life. BACKGROUND: Mechanical circulatory assistance with a left ventricular assist device is an accepted therapy for bridging patients with end-stage heart disease to heart transplantation and has been proposed for long-term implantation. METHODS: Three patients (aged 37, 42 and 57 years) with end-stage heart failure required implantation of a pneumatically driven, asynchronous Thermedics left ventricular assist device while awaiting heart transplantation. All were assessed 1 month later during graded supine bicycle exercise (maximal work load 100 to 150 W). Detailed central hemodynamics, including continuous pulmonary artery oxygen saturation and oxygen consumption measurements, were obtained. Two of the patients also underwent upright treadmill exercise with oxygen consumption measurements. RESULTS: During supine bicycle exercise, the heart rate increased from 93 +/- 37 beats/min (95% confidence interval: mean +/- t0.025 x SE) at rest to 119 +/- 54 beats/min and left ventricular assist device rate increased from 82 +/- 47 to 109 +/- 55 beats/min. Oxygen consumption increased from 3.0 +/- 0.9 to 8.7 +/- 2.9 ml oxygen/min per kg body weight. Cardiac output increased from 6.0 +/- 4.4 to 9.6 +/- 7.1 liters/min, yielding an average exercise factor of 8.5 +/- 7.7 and an exercise index of 0.83 +/- 0.61. The patients assessed during treadmill exercise achieved a maximal oxygen consumption of 14.3 and 16.7 ml of oxygen/min per kg. No thromboembolic or other complications attributable to left ventricular assist device implantation occurred during the duration of support. All patients survived orthotopic heart transplantation and are doing well. CONCLUSIONS: Significant work loads compatible with activities of daily life and adequate exercise hemodynamics were demonstrated by these patients while awaiting heart transplantation. Definitive conclusions regarding the use of this device must be viewed as preliminary because only three patients were involved in this study and the failure rate may be as high as 71% (95% confidence interval of left ventricular assist device success as a bridge to transplantation 29.3% to 100%). Final conclusions regarding the safety and efficacy of the left ventricular assist device as a possible long-term circulatory support device must await results of larger multicenter trials in progress.

Value of noninvasive testing in adults with suspected aortic stenosis.

To determine the predictors of surgically correctable aortic stenosis in patients with systolic murmurs, 231 patients were evaluated. Five variables (carotid upstroke timing, carotid upstroke volume, aortic valve calcification on chest radiography, single or absent second heart sound, and a murmur with its maximal intensity at the right upper sternal border) were significant multivariate correlates. Two echocardiographic factors (a maximal aortic valve leaflet separation of 7 mm or less and hypertrophy of the posterior wall of the left ventricle to 12 mm or more) and one systolic time interval factor (a rate-corrected ejection time of more than 340 msec) added significant incremental information. When prospectively tested on an independent set of 86 patients with suspected aortic outflow obstruction, the combined clinical and noninvasive information correctly placed 10 patients (12 percent) into a low-risk group in which catheterization may not be indicated and 15 patients (17 percent) into a high-risk group in which it might be avoided or limited to coronary arteriography. This approach to predicting aortic stenosis deserves wider prospective testing.

Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).

To analyze whether atherosclerotic risk factors, including systemic hypertension, an elevated serum cholesterol level, smoking and diabetes, were associated with the presence of aortic stenosis (AS) in adults, 105 adults who had AS without coronary artery disease (CAD) were compared with 110 control subjects who had other types of valvular disease, 170 control subjects who underwent catheterization and had neither valvular disease nor CAD, and 269 matched control subjects who underwent general surgery. When using each control group separately or in combination, no risk factor showed consistent evidence of a significant association with the development of AS. If the true magnitudes of these associations are of the order previously reported for the development of CAD, the power of our study for detecting statistical significance ranges from 56 to 99%. In a supplemental analysis, 45 cases with both AS and CAD did not have a higher prevalence of risk factors than cases without CAD. Although a weak association between atherosclerotic risk factors and AS cannot be excluded, any such association is unlikely to be as strong as for predicting CAD.

Characterization of pectin, flash-extracted from orange albedo by microwave heating, under pressure.

Pectin was acid extracted from orange albedo by microwave heating under pressure. Extraction times ranged from 2.5 to 8 min. Solubilized pectin was characterized for molar mass (M), rms radius of gyration (Rg) and intrinsic viscosity [eta] by HPSEC with online light scattering and viscosity detection. M, Rg and [eta] all decreased with increasing extraction time. Nevertheless, at heating times of 2.5 and 3.0 min, M, Rg and [eta] were significantly higher than a commercial citrus pectin when the albedo:solvent ratio was 1:25 (w/v). At the heating time of 2.5 min Mw was 3.6 x 10(5), Rgz was 38 nm and [eta]w was 10.8 dL/g. Chromatography revealed that solubilized pectin distributions were bimodal in nature and that the low-molar-mass fraction increased at the expense of the high-molar-mass fraction with increasing extraction time. Scaling law exponents revealed that the high-molar-mass fraction was extremely compact in shape, whereas the low-molar-mass fraction was more asymmetric in shape. Possibly these results indicated that at short extraction times, pectin was solubilized as compact aggregated network structures that were broken down to their more asymmetric components with increased heating times.

Left ventricular assist device support of medically unresponsive pulmonary hypertension and aortic insufficiency.

Most centers consider medically unresponsive pulmonary hypertension an absolute contraindication to orthotopic cardiac transplantation because the alternative surgical therapy, heterotopic graft placement, is associated with decreased survival, although most patients normalize their pulmonary hemodynamics postoperatively. Orthotopic transplantation in patients with elevated, but responsive pulmonary pressures, also is associated with an increased operative mortality rate and decreased long-term survival. The authors present the case of a patient with medically unresponsive pulmonary hypertension who was mechanically supported in an effort to improve his orthotopic transplant candidacy and decrease his risk. After informed consent, a HeartMate left ventricular assist device (LVAD) was inserted and the pulmonary hemodynamic response was monitored. Immediately before LVAD insertion, the pulmonary artery pressure (PA) was 74/28 mmHg with a transpulmonary gradient (TPG) of 28 mmHg, and a pulmonary vascular resistance (PVR) of 6.6 Wood units, despite prolonged dobutamine, milrinone, and prostaglandin E1 infusions. After 10 weeks of LVAD support, pressure and resistance improved; pulmonary artery pressure was 28/15 mmHg, transpulmonary gradient was 15 mmHg, and pulmonary vascular resistance was 2.8 Wood units. This patient subsequently underwent an uneventful orthotopic heart transplant. At 1 year after transplantation, pulmonary artery hemodynamics were normal (PA 34/14 mmHg, TPG at 8 mmHg, and PVR at 1.5 Wood units). The authors recommend the consideration of LVAD placement in patients with medically unresponsive pulmonary artery hypertension to assess PA responsiveness and improve the patient's orthotopic cardiac transplant candidacy and decrease the operative risk. However, several weeks may be needed for normalization of pressure and resistance.

Which patients with heart failure respond best to multidisciplinary disease management?

BACKGROUND: Multidisciplinary disease management approaches have been shown to decrease resource use in selected samples of patients with heart failure. We remain uncertain regarding the effectiveness of this approach in a general heart failure population and who can be expected to benefit most. The purpose of this study was to test the effectiveness of a multidisciplinary disease management intervention in an unselected population of patients with heart failure and to determine if subgroups could be identified in which the intervention is most effective. METHODS AND RESULTS: Two hundred forty patients with heart failure who were matched on preadmission functional status, comorbidity, and age participated in a quasi-experimental clinical trial. Half (n = 120) were given a multidisciplinary disease management intervention, whereas the other half (n = 120) received usual care. Data on acute care resource use were collected 3 and 6 months after enrollment. No intervention effect was seen in the primary analysis. When the data were analyzed by preadmission functional status (I to IV), acute care resource use was lower in the class II intervention patients. Class I intervention patients had a 288% increase in total costs and a 14-fold increase in heart failure costs. A model of predictor variables explained 17.2% of the variance in heart failure readmission at 3 months. CONCLUSIONS: An intervention of this type and intensity is recommended primarily for functional class II heart failure patients. Increases in cost in class I patients may have resulted from improved access to care.

Secondary structure of bovine alphaS2-casein: theoretical and experimental approaches.

Circular dichroism and Fourier transform infrared spectroscopy of bovine alphaS2-casein both report a 24 to 32% content of alpha-helix. A consensus of sequence based predictions for alpha-helix suggests a Lys77-Gln91 helix within the sequence (Ser61-Arg125). This motif is repeated at (Ser143-Leu207), and this region contains a longer Thr145-Leu177 predicted alpha-helix. A short, seven-member alpha-helix may also organize the N-terminal peptide that precedes the first phosphoserine [-Srp-]3 cluster. As was found for other caseins studied by these spectroscopic methods, a high degree of extended beta-sheet (approximately 30%) and turns (25 to 30%) are predicted for alphaS2-casein.

Particle sizes of purified kappa-casein: metal effect and correspondence with predicted three-dimensional molecular models.

kappa-Casein as purified from bovine milk exhibits a rather unique disulfide bonding pattern as revealed by SDS-PAGE. The disulfide-bonded caseins present range from dimer to octamer and above and preparations contain about 10% monomer. All of these heterogenous polymers, however, self-associated into nearly spherical uniform particles with an average radius of 8.9 nm as revealed by negatively stained transmission electron micrographs. Evidence is presented that multivalent cations play a role in the stabilization of these spherical particles. Treatment with EDTA causes disruption of the kappa-casein particles and leads to a broder size distribution as judged by electron microscopy and dynamic light scattering. The size and shape of the particles are in accord with earlier proposed 3D models for kappa-casein that actually predicted participation of divalent cations in the structure.

Implementation of a multidisciplinary disease management program for heart failure patients.

Institutions across the country are considering the feasibility of a disease management program for heart failure (HF) patients. Published reports suggest that such programs can save money and improve outcomes. However, the design of a disease management program can be challenging. This paper describes the structure and function of a successful disease management program for heart failure patients. The program is supported by a multidisciplinary team of nurses, pharmacists, dietitians, social workers, and physicians who approach the problem from a self care perspective. Program components include standardized educational materials, reinforcement of educational contacts, monthly support groups, and a quarterly newsletter. Existing staff built the program with few additional resources and staff. The program, which costs only approximately $330/patient for a 6 month intervention, has decreased hospital readmissions (29%) and days in the hospital (43%) significantly. (c)1999 by CHF, Inc.

Characterization of the particles of purified kappa-casein: trypsin as a probe of surface-accessible residues.

kappa-Casein as purified from bovine milk exhibits a rather unique disulfide bonding pattern as revealed by SDS-PAGE. The disulfide-bonded caseins present range from dimer to octamer and above and preparations contain about 10% monomer. All of these heterogeneous polymers, however, self-associate into nearly spherical particles with an average diameter of 13 nm at pH 8.0, as revealed by negatively stained transmission electron micrographs and dynamic light scattering. The weight-average molecular weight of the aggregates at pH 8.0, as judged by analytical ultracentrifugation, is 648,000. Trypsin digestion at pH 8.0 was used to probe the surface groups of the kappa-casein A polymers. The reaction with trypsin was rapid and the peptides liberated were identified by separation with reverse-phase HPLC, amino acid analysis, and protein sequencing. The most rapidly released peptides (t1/2 < 30 sec) were from cleavage at Arg 97 and Lys residues 111 and 112. These results suggest a surface orientation for these residues, and the data are in accord with earlier proposed 3D predictive models for kappa-casein. It is speculated that Arg 97, together with adjacent His residues (98 and 100) and Lys residues 111 and 112, form two positively charged clusters on the surface of the otherwise negatively charged casein. These clusters bracket the neutral chymosin cleavage site (whose hydrolysis triggers a well-known digestive process) and so these clusters may facilitate docking of the substrate caseins with chymosin.

Right and left ventricular function after cardiac transplantation. Changes during and after rejection.

BACKGROUND: Attempts to identify noninvasive markers of ventricular dysfunction accompanying acute rejection have been hampered by a lack of detailed simultaneous hemodynamic data. Therefore, we prospectively performed serial monitoring of detailed left and right heart hemodynamic parameters in cardiac transplant recipients at the time of routine endomyocardial biopsy to better define the physiology of the allograft heart during and after acute rejection. METHODS AND RESULTS: To better assess the pathophysiology of the rejection process, 18 cardiac transplant patients were prospectively studied by serial right heart micromanometer catheterization and digital image processing at the time of routine endomyocardial biopsy. Eleven patients had 18 episodes of rejection. Studies of baseline (negative biopsy preceding rejection), rejection (acute moderate rejection), and resolved (first negative biopsy after rejection) states were compared. Seven patients who did not experience an episode of rejection served as the control group. Right ventricular minimum and end-diastolic pressures increased from baseline values of 0.9 +/- 3.2 and 6.9 +/- 3.7 mm Hg, respectively, to 3.2 +/- 5.5 and 9.9 +/- 6.6 mm Hg, respectively, with rejection (both variables, p less than 0.05) and remained elevated despite histological resolution of rejection (4.3 +/- 5.5 and 10.0 +/- 7.1 mm Hg, respectively; p less than 0.05 for both variables compared with baseline values). Concurrently, right ventricular end-diastolic volumes (133 +/- 29, 119 +/- 27, and 114 +/- 30 ml; baseline, rejection, and resolved, respectively) and left ventricular end-diastolic volumes (133 +/- 24, 117 +/- 20, and 113 +/- 30 ml; baseline, rejection, and resolved, respectively) significantly decreased during rejection and remained decreased after resolution of rejection (rejection and resolved compared with baseline values, p less than 0.05). Right ventricular chamber stiffness (0.055 +/- 0.035, 0.085 +/- 0.057, and 0.092 +/- 0.076 mm Hg/ml; baseline, rejection, and resolution, respectively; rejection and resolved compared with baseline values, p less than 0.05) increased with rejection and remained elevated after resolution of rejection. Right ventricular peak filling rate also increased from a baseline value of 2.48 +/- 0.45 to 2.76 +/- 0.63 ml end-diastolic volumes per second with rejection (p less than 0.05). Elevation of right ventricular filling pressures, peak filling rate, and chamber stiffness with a concomitant decrease in end-diastolic volume is consistent with a restrictive/constrictive physiology. Mean arterial blood pressure and systemic vascular resistance were elevated after the resolution of rejection (compared with either rejection or baseline values, p less than 0.05) associated with a higher mean daily dose of prednisone (resolved compared with either baseline or rejection values, p less than 0.05). The control group experienced a time-dependent increase in mean and diastolic systemic arterial pressures (both comparisons, p less than 0.05) without detectable diastolic dysfunction. CONCLUSIONS: Persistence of biventricular diastolic dysfunction may be due to an irreversible effect of rejection, although multifactorial changes in left ventricular afterload occur that may complicate serial assessment of ventricular function.