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Background: Existing research demonstrates superior short-term outcomes (length of stay, 1-year survival) after lung transplantation in patients with preoperative functional independence. The aim of this study was to determine whether advantages remain significant in the long-term., Methods: The United Network for Organ Sharing database was queried for adult, first-time, isolated lung transplantation records from January 2005 to December 2015. Stratification was performed based on Karnofsky Performance Status Score (3 groups) and on employment at the time of transplantation (2 groups). Kaplan-Meier and Cox analyses were performed to determine the association between these factors and survival in the long-term., Results: Of 16,497 patients meeting criteria, 1,581 (9.6%) were almost completely independent at the time of transplant vs 5,662 (34.3%) who were disabled (completely reliant on others for activities of daily living). Cox models adjusting for recipient, donor, and transplant factors demonstrated a statistically significant association between disability at the time of transplant and long-term death (hazard ratio, 1.26; 95% confidence interval, 1.14 to 1.40; p < 0.001). There were 15,931 patients with available data on paid employment at the time of transplantation. Multivariable analysis demonstrated a statistically significant association between employment at the time of transplantation and death (hazard ratio, 0.86; 95% confidence interval, 0.75 to 0.91; p < 0.001)., Conclusions: Preoperative functional independence and maintenance of employment are associated with superior long-term outcomes in lung recipients. The results highlight potential benefits of pretransplant functional rehabilitation for patients on the waiting list for lungs., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anticoagulation is difficult due to bleeding. A novel "cytotopic" agent, thrombalexin (TLN), combines a cell-membrane-bound (myristoyl tail) anti-thrombin (hirudin-like peptide [HLL]), which can be perfused directly to the donor organ or cells. Thromboelastography was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN versus HLL (without cytotopic tail) versus negative control. Both TLN- and HLL-treated rhesus or human whole blood result in significantly prolonged r-time compared to kaolin controls. Only TLN-treated human endothelial cells and neonatal porcine islets prolonged time to clot formation. Detection of membrane-bound TLN was confirmed by immunohistochemistry and fluorescence activated cell sorter. In vivo, perfusion of a nonhuman primate kidney TLN-supplemented preservation solution in a sensitized model of transplantation demonstrated no evidence of TLN systemically. Histologically, TLN was shown to be present up to 4 days after transplantation. There was no platelet deposition, and TMA severity, as well as microvascular injury scores (glomerulitis + peritubular capillaritis), were less in the TLN-treated animals. Despite promising evidence of localized efficacy, no survival benefit was demonstrated., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity form and a transient, high-affinity form, expressed only during activation. We have shown that antibodies reactive with LFA-1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL-579, each of which targets the high-affinity form of LFA-1, to determine whether this more precise targeting prevents belatacept-resistant rejection. Despite evidence of ex vivo and in vivo ligand-specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL-579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA-1 blockade may not be a suitable adjuvant agent for CoB-resistant rejection., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Comprehensive understanding of the transport and deposition of engineered nanoparticles (NPs) in subsurface is required to assess their potential negative impact on the environment. We studied the deposition behavior of functionalized quantum dot (QD) NPs (CdTe) in different types of sands (Accusand, ultrapure quartz, and iron-coated sand) at various solution ionic strengths (IS). The observed transport behavior in ultrapure quartz and iron-coated sand was consistent with conventional colloid deposition theories. However, our results from the Accusand column showed that deposition was minimal at the lowest IS (1mM) and increased significantly as the IS increased. The effluent breakthrough occurred with a delay, followed by a rapid rise to the maximum normalized concentration of unity. Negligible deposition in the column packed with ultrapure quartz sand (100mM) and Accusand (1mM) rules out the effect of straining and suggests the importance of surface charge heterogeneity in QD deposition in Accusand at higher IS. Data analyses further show that only a small fraction of sand surface area contributed in QD deposition even at the highest IS (100mM) tested. The observed delay in breakthrough curves of QDs was attributed to the fast diffusive mass transfer rate of QDs from bulk solution to the sand surface and QD mass transfer on the solid phase. Scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis were used to examine the morphology and elemental composition of sand grains. It was observed that there were regions on the sand covered with layers of clay particles. EDX spectra collected from these regions revealed that Si and Al were the major elements suggesting that the clay particles were kaolinite. Additional batch experiments using gold NPs and SEM analysis were performed and it was observed that the gold NPs were only deposited on clay particles originally on the Accusand surface. After removing the clays from the sand surface, we observed negligible QD deposition even at 100mM IS. We proposed that nanoscale charge heterogeneities on clay particles on Accusand surface played a key role in QD deposition. It was shown that the value of solution IS determined the extent to which the local heterogeneities participated in particle deposition., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Monitoring of environmental contaminants in Canadian Arctic polar bears (Ursus maritimus) typically has used superficial adipose tissue samples collected as part of controlled native subsistence hunts. However, little attention has been paid to the compositional difference in contaminants that may exist among the major adipose depots that are routinely collected. To address this knowledge gap, we investigated the profiles and concentrations of chlorinated hydrocarbon contaminants (CHCs), including major polychlorinated biphenyl (PCB) congeners and organochlorine (OC) pesticides and metabolites, in six major adipose depots (i.e. superficial, inter-muscular and intra-abdominal regions) obtained from adult male polar bears in the vicinity of Resolute Bay, Canadian high Arctic. Concentrations and congener patterns of PCBs (20 congeners) and OCs (14 compounds; chlordanes and dichlorodiphenyltrichloroethanes and metabolites, chlorinated benzenes, hexachlorocyclohexane isomers, octachlorostyrene and dieldrin) were found to be relatively uniform throughout the adipose tissue of male polar bears. The only exception was the inter-muscular adipose depot from the cervical region, which was characterized, compared to other major depots routinely sampled, by lower proportions of higher-chlorinated and recalcitrant congeners such as CB170/190, 180, 194 and 206, and higher contribution of the lower-chlorinated PCBs, CB47, 74 and 99. No difference in the OC makeup and concentrations was found among the adipose depots investigated. In view of this, we conclude that the determination of CHCs in adipose tissue of polar bears from any major depots, with the potential exception of the fat under the neck muscles, would give a representative picture of the overall CHC composition and concentrations in polar bear fat for purpose of trend monitoring.

Study Objective: Exercise has the potential to improve the ability of a patient with cystic fibrosis (CF) to cope with the physical demands of everyday life, and may improve prognosis. The purpose of this study was to compare the effects of a home-based, semi-supervised, upper-body strength-training regimen with a similarly structured aerobic training regimen., Design: Data were collected during a 1-year randomized clinical trial., Setting: Counselors conducted in-home visits with the participants once per week for the first 8 weeks followed by monthly visits for the remainder of the study., Patients: Sixty-seven patients with CF, aged 8 to 18 years, participated in the trial., Intervention: Participants in both exercise conditions were encouraged to exercise at least three times per week for 1 year. Each child in the aerobic group was given a stair-stepping machine, and each child in the upper-body strength training group was given an upper-body-only weight-resistance machine., Measures and Results: Aerobic fitness, pulmonary function, quality of life, and strength were measured at baseline, at 6 months, and at 12 months. Strength training increased the maximum weight lifted for biceps curls significantly more than aerobic training (p < 0.02). However, this differential did not remain significant after control for increase in height. Both training procedures were associated with increased strength (p < 0.002) and physical work capacity (PWC) [p < 0.033]., Conclusions: We concluded that strength and aerobic training may increase upper-body strength, and that both types of training may increase PWC for children with CF. Future trials should be conducted with no-training control subjects and larger samples to increase statistical power.

Decisions about care at the end of life are not only influenced by doctor-patient-family relationships and physician practice, but also by institutional "culture." An institutional assessment of the quality of care provided to dying hospitalized patients was undertaken to characterize and identify factors influencing it and to find opportunities for improvement. An analysis of hospital data, three physician and nursing focus group discussions, structured review of records of targeted patients (61) who had an "expected death," and interviews with 31 surviving family members of the targeted patients served as the basis for an institutional needs assessment intended to precede the development of a quality improvement program to improve hospital care of patients at the end of life. Data were primarily gathered regarding older adults, including a significant number of nursing home residents. The assessment led to a methodology for developing a quality improvement program based upon feedback to physicians and nurses regarding the quality of end-of-life care.

Study Objectives: To assess the validity of purified protein derivative (PPD) readings by patients and trained health-care professionals as compared with a calibrated model., Design and Participants: Survey of a group of patients, nurses, medical assistants, and physicians at five neighborhood health centers in the Bronx, NY., Interventions: Participants were asked to read a calibrated model with four PPD indurations measuring 0 mm, 3 mm, 7 mm, and 13 mm. Indurations > or = 5 mm were to be considered "positive" reactions., Measurements and Results: Data were obtained from 233 patients and 80 trained professionals. All patients correctly measured the 0-mm induration site and were able to detect the presence of an induration in 99.3% of possible observations. Compared with professionals, patients had more variability in measurements and interpretations of the 3-, 7-, and 13-mm sites. Professionals detected 100% of all indurations. Patients' specificity for the 0- and 3-mm sites was 97.4% and 62.7%, respectively; whereas sensitivity for the 7- and 13-mm sites was 68.2% and 89.3%, respectively. Professionals' specificity for the 0- and 3-mm sites was 98.7% and 65.3%, respectively; their sensitivity for the 7- and 13-mm sites was 86.7% and 97.3%, respectively. Seventy percent of professionals agreed that the model was a realistic representation of PPD indurations., Conclusions: Patients can reliably distinguish between the presence and absence of an induration at a PPD injection site. They are not as reliable in the measurement and interpretation of test reactions. Professionals had considerable variability in their assessments of PPDs but were more precise overall in their assessments than patients.

Many people on the waiting list for organ donation die each year without receiving organs. The shortage of organs is even more pronounced in minority communities. Despite the fact that minorities are at higher risk, they may be less likely to support or consent to organ donation. This investigation was undertaken to study racial factors in organ donation, by focusing on differences in awareness, attitudes, and behavior. Three family practice centers in the Bronx with racially diverse but socioeconomically homogenous communities were studied. The study population consisted of a convenience sample of 163 patients who were approached for participation while they waited to see a doctor. Respondents filled out a 25-item survey that measured demographic information; their exposure to, awareness of, and attitudes toward organ donation; and whether they had signed an organ donor card. The results demonstrated overwhelming support for organ donation across all racial groups. Racial differences were found on awareness of and attitudes toward organ donation, and in the signing of organ donation cards. In contrast to other studies, racial minorities were not less likely than whites to support organ donation. These results suggest that making it easier for racial minorities to obtain organ donor cards could increase their rates of consenting to donate organs.

A health seminar seemed to modify knowledge, attitudes, and reported behavior of a self-selected audience which was already well informed and motivated to change. Therefore, the health seminar appears to be a useful educational approach in this context. The question remains: How can those who are neither informed nor motivated be reached? This study suggests that the public seminar may not be an efficient vehicle for this purpose.