Tropical seabirds sample broadscale patterns of marine contaminants.

Contaminants in the marine environment are widespread, but ship-based sampling routines are much narrower. We evaluated the utility of seabirds, highly-mobile marine predators, as broad samplers of contaminants throughout three tropical ocean regions. Our aim was to fill a knowledge gap in the distributions of, and processes that contribute to, tropical marine contaminants; and explore how species-specific foraging ecologies could inform or bias our understanding of contaminant distributions. Mercury and persistent organic pollutant (POPs) concentrations were measured in adults of five seabird species from four colonies in the central Pacific (Laysan and Tern Islands, Hawaii; Palmyra Atoll) and the eastern Caribbean (Barbuda). Blood-based total mercury (THg) and 89 POPs were measured in two seabird families: surface-foraging frigatebirds (Fregata spp.) and plunge-diving boobies (Sula spp.). Overall, largescale contaminant differences between colonies were more informative of contaminant distributions than inter-specific foraging ecology. Model selection results indicated that proximity to human populations was the best predictor of THg and POPs. Regional differences in contaminants were distinct: Barbudan Magnificent Frigatebirds had more compounds (n=52/89 POP detected) and higher concentrations (geometric mean THg=0.97µgg-1; mean ΣPOP53=26.6ngmL-1) than the remote colonies (34-42/89 POP detected; range of THg geometric means=0.33-0.93µgg-1; range of mean ΣPOP53:7.3-17.0ngmL-1) and had the most recently-synthesized POPs. Moderate differences in foraging ecologies were somewhat informative of inter-specific differences in contaminant types and concentrations between nearshore and offshore foragers. Across species, contaminant concentrations were higher in frigatebirds (THg=0.87µgg-1; ΣPOP53=17.5ngmL-1) compared to boobies (THg=0.48µgg-1; ΣPOP53=9.8). Ocean currents and contaminants' physiochemical properties provided additional insight into the scales of spatial and temporal contaminant exposure. Seabirds are excellent, broad samplers with which we can understand contaminant distributions in the marine environment. This is especially important for tropical remote regions that are under-sampled.

Temporal and interspecific variation in feather mercury in four penguin species from Macquarie Island, Australia.

We measured mercury (Hg) concentrations in feathers from four penguin species collected on Macquarie Island, Southern Ocean, to 1) establish baseline Hg concentrations; and 2) compare Hg from samples collected in 2002 ("modern") and from museum specimens collected between 1937 and 1976 ("historic"). Inter-specific differences in feather Hg reflected known differences in habitats and diversity of diets: benthic-foraging Gentoo penguins and Rockhopper penguins that foraged both inshore and offshore had significantly higher feather mercury than the more pelagic, specialist foraging King and Royal penguins. Hg significantly decreased between historic and modern samples in King and Royal penguins. This decrease could be due to changes in either diet, foodwebs, or atmospheric Hg input and sources in the Southern Hemisphere. Because Macquarie Island is home to 2.8 million marine animals, these data may indicate that other species that forage and breed in this region are also exposed to low Hg concentrations in this environment.

Mood, body image, fear of kidney failure, life satisfaction, and decisional stability following living kidney donation: Findings from the KDOC study.

Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.

Vascularized Composite Allograft Donation and Transplantation: A Survey of Public Attitudes in the United States.

Vascularized composite allograft (VCA) transplantation has emerged as a groundbreaking surgical intervention to return identity and function following traumatic injury, congenital deformity, or disfigurement. While public attitudes toward traditional organ/tissue donation are favorable, little is known about attitudes toward VCA donation and transplantation. A survey was conducted of 1485 U.S. residents in August 2016 to assess VCA donation attitudes. Participants also completed the Revised Health Care System Distrust Scale. Most respondents were willing to donate hands/forearms (67.4%) and legs (66.8%), and almost half (48.0%) were willing to donate the face. Three-quarters (74.4%) of women were willing to donate the uterus; 54.4% of men were willing to donate the penis. VCA donation willingness was more likely among whites and Hispanics (p < 0.001), registered organ/tissue donors (p < 0.001), and those with less health care system distrust (p < 0.001) and media exposure to VCA transplantation (p = 0.003). Many who opposed VCA donation expressed concerns about psychological discomfort, mutilation, identity loss, and the reaction of others to seeing familiar body parts on a stranger. Attitudes toward VCA donation are favorable overall, despite limited exposure to VCA messaging and confusion about how VCA donation occurs. These findings may help guide the development and implementation of VCA public education campaigns.

Health Insurance Trends in United States Living Kidney Donors (2004 to 2015).

Some transplant programs consider the lack of health insurance as a contraindication to living kidney donation. Still, prior studies have shown that many adults are uninsured at time of donation. We extend the study of donor health insurance status over a longer time period and examine associations between insurance status and relevant sociodemographic and health characteristics. We queried the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry for all living kidney donors (LKDs) between July 2004 and July 2015. Of the 53 724 LKDs with known health insurance status, 8306 (16%) were uninsured at the time of donation. Younger (18 to 34 years old), male, minority, unemployed, less educated, unmarried LKDs and those who were smokers and normotensive were more likely to not have health insurance at the time of donation. Compared to those with no health risk factors (i.e. obesity, smoking, hypertension, estimated glomerular filtration rate <60, proteinuria) (14%), LKDs with 1 (18%) or ≥2 (21%) health risk factors at the time of donation were more likely to be uninsured (p < 0.0001). Among those with ≥2 health risk factors, blacks (28%) and Hispanics (27%) had higher likelihood of being uninsured compared to whites (19%; p < 0.001). Study findings underscore the importance of providing health insurance benefits to all previous and future LKDs.

Direct and Indirect Costs Following Living Kidney Donation: Findings From the KDOC Study.

Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman's ρ = 0.26, p < 0.001), lower household income (Spearman's ρ = -0.25, p < 0.001), and more unpaid work hours missed (Spearman's ρ = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large.

Autonomous dysregulation of orthostatic disorders in young individuals engaged into manual work.

The authors analyzed changes of statistic, spectral and non-linear parameters of cardiac rhythm variability in response to active orthostasis test in young individuals engaged into manual work, and the results are compared with hemodynamic parameters. Evidence is that the patients with neurogenous fainting present sympathetic vasomotory regulation disorders even in young age; before clinical manifestation as orthostatic hypotension. In comparison with common tilt-test, spectral analysis of cardiac rhythm variability in active orthostatic test can be more useful to reveal early disorders of autonomous regulation.

Predonation Direct and Indirect Costs Incurred by Adults Who Donated a Kidney: Findings From the KDOC Study.

Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate's family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them.

Organ donation video messaging: differential appeal, emotional valence, and behavioral intention.

Video narratives increasingly are used to draw the public's attention to the need for more registered organ donors. We assessed the differential impact of donation messaging videos on appeal, emotional valence, and organ donation intentions in 781 non-registered adults. Participants watched six videos (four personal narratives, one informational video without personal narrative, and one unrelated to donation) with or without sound (subtitled), randomly sequenced to minimize order effects. We assessed appeal, emotional valence, readiness to register as organ donors, and donation information-seeking behavior. Compared to other video types, one featuring a pediatric transplant recipient (with or without sound) showed more favorable appeal (p < 0.001), generated more positive emotional valence (p < 0.01), and had the most favorable impact on organ donor willingness (p < 0.001). Ninety-five (12%) participants clicked through to a donation website after viewing all six videos. Minority race (OR = 1.94, 95% CI = 1.20, 3.13, p = 0.006), positive change in organ donor readiness (OR = 0.26, 95% CI = 0.14, 0.48, p < 0.001), and total positive emotion (OR = 1.05, 95% CI = 1.03, 1.07, p < 0.001) were significant multivariable predictors of clicking through to the donation website. Brief, one-min videos can have a very dramatic and positive impact on willingness to consider donation and behavioral intentions to register as an organ donor.

Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer.

Anaemia is a common haematologic disorder in patients with cancer and has a multifactorial aetiology, including the effects of the malignancy itself and residual effects from previous therapy. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa), a protein with additional sialic acid compared with erythropoietin (EPO), stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO) but it is biochemically distinct. NESP, with its approximately 3-fold greater serum half-life, can maintain haemoglobin levels as effectively as rHuEPO in anaemic patients with chronic renal failure and do so with less frequent dosing. We investigated the ability of NESP to safely increase haemoglobin levels of anaemic patients with non-myeloid malignancies not receiving chemotherapy. NESP was administered under the supervision of a physician at doses of 0.5, 1.0, 2.25 or 4.5 mcg kg(-1)wk(-1)for a maximum of 12 weeks. This report includes 89 patients completing the study by November 2000. NESP was well tolerated, with no reported dose-limiting toxicities or treatment-related severe adverse events. Increasing doses of NESP corresponded with increased efficacy. The percentage (95% confidence interval) of patients responding ranged from 61% (42%, 77%) in the 1.0 mcg kg(-1)wk(-1)group to 83% (65%, 94%) in the 4.5 mcg kg(-1)wk(-1)group.

[The novel method for selection of preparations for treatment of arterial hypertension based on spectral analysis of heart rhythm variability]. / Novyi sposob podbora preparatov dlia lecheniia arterial'noi gipertonii na osnove spektral'nogo analiza variabel'nosti ritma serdtsa.

AIM: To study spectral characteristics of heart rhythm in patients with arterial hypertension (AH) to select medication for hypertension and control over the treatment efficacy. MATERIAL AND METHODS: 35 AH patients were examined with general clinical methods and using spectral analysis of variability of heart rhythm (VHR). Five spectrograms were registered. Each of them contained three peaks: very low, low and high frequencies (VLF, LF and HF, respectively). Normal values of VLF, LF and HF were estimated on the basis of spectral values obtained in healthy subjects. After registration of spectral values all the patients were given at first placebo, than enalapril, one day after its discontinuation--mifedipine. At each stage VHR was recorded. Changes in the spectral indices were compared to changes in clinical symptoms. RESULTS: VLF proved most important for a rapid choice of adequate antihypertensive therapy. CONCLUSION: Normalization of VLF, LF and HF indicates adequacy of the choice of antihypertensive treatment.

A randomized study of the safety and antiretroviral activity of hydroxyurea combined with didanosine in persons infected with human immunodeficiency virus type 1. American Foundation for AIDS Research Community-Based Clinical Trials Network.

This randomized open-label trial of human immunodeficiency virus type 1-infected persons compared safety and efficacy for 38 patients receiving hydroxyurea/didanosine combination therapy with findings in 42 persons given didanosine monotherapy for 12 weeks, followed by 12 weeks of hydroxyurea/didanosine combination therapy for all patients. Week 12 on-treatment group comparisons showed a mean decrease in virus load between hydroxyurea/didanosine versus didanosine groups of -0.93 versus -0.74 log10 copies/mL (P=.20); a higher percentage of the hydroxyurea/didanosine group below the assay's detection limit (500 copies/mL), 29% versus 7% (P=.017); and median change in CD4 cells for the hydroxyurea/didanosine versus didanosine group of 0 versus 43 cells/mm3 (P=.045), although median change in CD4 percentage was similar (0.9% vs. 1.2%, P=.64). Week 24 virus load reductions and CD4 cell changes were similar in both groups. Intent-to-treat and on-treatment analyses showed similar results. The hydroxyurea/didanosine combination was well tolerated.

BCL-X expression in multiple myeloma: possible indicator of chemoresistance.

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.

Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and rhesus monkey using nasal molds: relevance to formaldehyde toxicity.

For highly water soluble and reactive gases, such as formaldehyde, the reported distribution of nasal lesions in rats and rhesus monkeys following inhalation exposure may be attributable, at least in part, to regional gas uptake patterns that are a consequence of nasal airflow characteristics. Inspiratory nasal airflow was studied at flow rates across the physiologic range using a unidirectional dynamically similar water-dye siphon system in clear acrylic molds of the nasal airways of F344 rats and rhesus monkeys. In both species there were complex and inspiratory flow streams, exhibiting regions of simple laminar, complex secondary (vortices, eddies, swirling), and turbulent flows, with only minor effects of the volumetric flow rates studied on these flow patterns. There was a precise association between points of dye intake at the nostril with complex but generally coherent streaklines throughout the nose, indicating the potential for sensitive dependence of nasal airflow on nostril geometry. On the basis of these studies, a classification for the major airways (meatuses) in the nasal passages of rats and rhesus monkeys was proposed. The spiral shape of the anterior nasal airway of the rat was considered to play an important role in local mixing of inspired airstreams. In the rhesus monkey, the complex geometry of the nasal vestibule contributed to the formation of secondary flows and turbulence in the anterior nose, which represents a potentially important difference between rheusus monkeys and humans. There was a good correlation between routes of flow, regional secondary flows, turbulence, and impaction of airstreams on the airway wall, with the reported distribution of formaldehyde-induced nasal lesions in rats and rhesus monkeys. These studies support the proposal that nasal airflow patterns play an important role in the distribution of lesions induced by formaldehyde.

Cost benefit analysis of radiological protection: a case study of remote after-loading in gynaecological radiotherapy.

The ICRP system of dose limitation requires radiation exposures to be kept "as low as reasonably achievable" (ALARA). The International Commission on Radiological Protection (ICRP) advocates a form of cost benefit analysis for this purpose, in which a comparison is made between the costs of protective measures and the benefits of reduced radiation exposure. In the UK, the National Radiological Protection Board (NRPB) has been developing a framework for the practical application of cost benefit techniques to aid the evaluation of investments in radiological protection. One such investment, being undertaken at a number of radiotherapy centres, concerns remote after-loading equipment to replace the use of radium in the treatment of gynaecological cancers. The introduction of such equipment can offer a complete solution to the radiological protection problems associated with manual radium insertions but involves large capital expenditures on equipment and shielded treatment rooms. This paper describes a cost benefit analysis of introducing remote after-loading equipment at the Christie Hospital and Holt Radium Institute in Manchester. In accordance with the NRPB framework, it is shown that the introduction of after-loading equipment, when housed in appropriately protected rooms, should result in a substantial net benefit and would therefore be justified on radiological protection grounds according to the ALARA principle.