Foraging Ecology Differentiates Life Stages and Mercury Exposure in Common Terns (Sterna hirundo).

Some populations of common terns (Sterna hirundo) breeding at inland lakes in North America are declining, including the Laurentian Great Lakes. Terns nesting at inland colonies forage in freshwater during the breeding season and primarily in coastal marine environments during the nonbreeding season. As piscivores, they are susceptible to dietary Hg exposure. To characterize patterns of Hg exposure in this population, we 1) quantified within and among season differences in total mercury (THg) concentrations (µg/g) in blood and feathers at 2 Lake Superior breeding colonies, and 2) documented spatial and temporal variation in exposure by studying adult foraging ecology using geospatial tracking devices and stable isotopes. We used general linear models to assess the relationship between isotopic composition and THg concentrations in bird tissues relative to sex, age, colony location, and season. The THg concentrations were lowest in winter-grown feathers (geometric mean [95% confidence limits]): 1.32 (1.09-1.59) µg/g dw (n = 60), higher at the more industrially influenced colony (chick feathers: 4.95 [4.62-5.37] µg/g dw [n = 20]), and increased with a riverine-based diet. During the breeding season, Hg exposure varied along a gradient from lake to river, with adult females having lower blood THg concentrations than males (females: 0.83 [0.67-1.03]) µg/g ww (n = 7); males: 1.15 (0.92-1.45) µg/g ww (n = 5). Stable isotope values suggested adults obtained 42 ± 12% (n = 12) of their diet from the river during incubation, which was validated with tracking data. During chick-rearing, chicks obtained 68 ± 19% (n = 44) of their diet from the river. Our results indicate colony location, foraging behavior, and season influenced Hg exposure for these Lake Superior colonies and underscores the importance of local contamination with respect to exposure. Integr Environ Assess Manag 2021;17:398-410. © 2020 SETAC.

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo.

We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was confirmed by RT--PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated filters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.

The clinical utility of blood pressure load in hypertension.

The variability of blood pressure and its consequences suggests that ambulatory blood pressure (ABP) data should be analyzed not only by mean ambulatory blood pressure (MABP), but also by looking at blood pressure load (BPL, the percentage of measurements > 140/90 mm Hg while awake and > 120/80 while asleep). In one study, several hypertensive patients whose ambulatory diastolic blood pressure was < 90 mm Hg had a diastolic load near 50%. Studies have reported strong correlations between BPL and indices of target-organ changes such as left ventricular mass index (LVMI). It was necessary to lower office blood pressure to < 85 mm Hg to reduce BPL to a normal range of 15 to 20%. To further investigate the usefulness of BPL in the study of hypertension, more longitudinal studies of cardiovascular disease and blood pressure variability are needed.

Recapping the accidental needlestick problem.

A funnel-shaped shield of 1 to 2 cm diameter at the mouth of a needle cap is shown to be effective at decreasing the number of accidental misses occurring in a recapping trial. An argument is made for recapping needles and incorporating new needle cap designs in a revision of the CDC guideline on needle disposal.

How many lymph nodes are enough during sentinel lymphadenectomy for primary melanoma?

BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to reliably identify nodal metastases and the subsequent need for further surgical and adjuvant therapy in patients with cutaneous melanoma. Although SLN identification rates have improved with the addition of radioactive colloid to the blue dye technique, it remains unclear how many lymph nodes should be removed to accurately determine the histologic status of the nodal basin. The objective of this study was to determine the optimal extent of SLN biopsy in these patients. METHODS: The records of 633 consecutive patients with melanoma (765 nodal basins) whose primary treatment included SLN biopsy with the use of a combination of blue dye and technetium Tc 99 labeled sulfur colloid were reviewed. SLN biopsy consisted of the removal of all of the blue-stained nodes and all nodes with radiotracer uptake activity of at least twice background. RESULTS: SLN biopsy was successful in 765 of 772 basins (99%). A mean of 1.9 SLNs (median, 2 SLNs) per basin were excised. At least 3 SLNs were removed in 176 basins (23%). The overall histologic status of a basin was always established by the first or second SLN harvested (ie, in no patient was the third or subsequent SLN positive when 1 of the first 2 was not). Of the 124 basins containing lymphatic metastases, the SLN that contained the maximal radiotracer uptake (hottest) and/or stained blue was pathologically positive in 118 basins (95%). In only 6 of the 124 positive basins (5%) was the sole evidence of occult nodal metastases identified in an SLN that was neither blue-stained nor the hottest. All but 1 of these SLNs had counts that were at least 66% of the hottest node in the basin. CONCLUSIONS: With a combined modality approach to SLN biopsy, removal of more than 2 SLNs did not provide information that upstaged any patient with primary melanoma. Removal of additional nonblue SLN(s) that contained radioactive counts of at least twice background but lower than two thirds of the SLNs with maximal radiotracer uptake affected patient management in less than 0.2% of all cases. These findings may be helpful in minimizing the extent of surgery and perhaps in reducing the costs and resource use associated with operating room time and pathologic examination.

Parents' utilities for outcomes of occult bacteremia.

OBJECTIVE: To describe parents' values for outcomes of occult bacteremia using utility assessment, a quantitative method that incorporates risk preference. DESIGN: Computer-based utility assessment interview. SETTING: Urban children's hospital pediatric emergency department with 50 000 visits annually. PARTICIPANTS: Convenience sample of parents presenting with a child between 3 and 36 months. MAIN OUTCOME MEASURE: Parents' utility values for 8 outcomes from treatment of occult bacteremia: blood drawing, localized infection, hospitalization for antibiotics, meningitis with recovery, meningitis resulting in deafness, minor brain damage, severe brain damage, and death. RESULTS: Ninety-four subjects successfully completed the interview. Mean utilities were 0.9974 for blood drawing, 0.9941 for local infection, 0.9921 for hospitalization, 0.9768 for meningitis with recovery, 0.8611 for deafness, 0.7393 for minor brain damage, 0.3903 for severe brain damage, and 0.0177 for death. All values were significantly different from those that immediately preceded and succeeded (P<.0001), except for local infection vs hospitalization (P = .14). Median utilities for blood drawn, local infection, and hospitalization were 1. There were no significant differences among utilities of parents who presented with a febrile child (temperature > or =39 degrees C), or an afebrile child (temperature <39 degrees C). There were also no significant differences among utilities regardless of whether parents had children with prior experience with the outcomes. CONCLUSIONS: Assessment of utilities for outcomes of occult bacteremia yielded extremely high mean and median values for outcomes without permanent sequelae. This suggests that parents presenting to an emergency department may rationally prefer painful transient experiences, including venipuncture, for their children rather than risk even rare chances of severe outcomes.

Assessing the preferences of patients with psoriasis. A quantitative, utility approach.

BACKGROUND AND DESIGN: Patient preferences for health outcomes can be explicitly assessed and expressed in quantitative terms known as utilities. Three standard methods for utility assessment have been used to quantify patient preferences, but these methods have not previously been applied to skin disease. Eighty-seven patients with psoriasis from a tertiary medical center were interviewed, using an interactive, computer-based utility assessment questionnaire, U-Titer. Utilities for three categories of psoriasis severity and potential adverse outcomes of methotrexate therapy were assessed by the vertical rating scale, time trade-off, and standard gamble. RESULTS: Patients assigned a broad range of utilities for each of the health states. Utilities obtained by the vertical rating scale did not correlate well with utilities obtained by standard gamble or time trade-off methods. However, utilities assessed by standard gamble and time trade-off were not significantly different. Patient characteristics such as age, gender, and education were not correlated with utility and did not explain the variation. Indicators of the patients' disease severity were not predictive of utilities for the assessed health states. The relatively high utility for liver biopsy suggests that there is less patient aversion to the procedure than suspected. CONCLUSIONS: Utilities, or quantitative measures of patient preferences for health states, are measurable and vary widely for mild, moderate, and severe psoriasis and possible adverse outcomes of methotrexate treatment. The process of elucidating individual patient utilities for various health outcomes can be used to incorporate patient preferences into the process of clinical decision making. Guidelines that are based solely on severity of symptoms, without input from patients on how they value such symptoms, must be questioned.

Variability in platelet procoagulant activity in healthy volunteers.

Blood platelets provide the major surface for thrombin generation. When platelets are activated they expose phosphatidylserine (PS) on their outer membranes, providing the surface on which two procoagulant enzyme complexes, the Xase and prothrombinase complexes, assemble. We hypothesized that there is biological variability in platelet procoagulant activity. To test this hypothesis, we activated isolated platelets from seventeen volunteers, and added plasma concentrations of factors VIII, IXa, and X for the Xase complex assembly, and F.Xa and II for the prothrombinase complex. Xase and prothrombinase activity were assayed using a chromogenic substrate. We found a two- to three-fold variation in Xase and prothrombinase activity, respectively. The distribution of Xase activity in the population was symmetric, while the distribution of prothrombinase activity was positively skewed. The difference in distribution implies that simple expression of procoagulant lipid was not the only determinant of procoagulant activity. Variation in prothrombinase activity was not due to the amount of platelet-released F.V. Neither microparticle production nor F.X binding correlated with Xase or prothrombinase activity. Using fluorescein-conjugated annexin V, we also found no direct correlation between the level of PS exposure and Xase or prothrombinase activity. This indicates that platelets must make other contributions, in addition to PS, to the activity of the Xase and prothrombinase complexes. There is evidence that platelets possess specific receptors for some coagulation proteins, although these receptors have not been isolated. Biological variability in the expression of platelet receptors might explain the differences in Xase and prothrombinase activities in our study.

Bipyrimidine-Bridged Mixed-Metal Trimetallic Complexes of Ruthenium(II) with Rhodium(III) or Iridium(III), {[(bpy)(2)Ru(bpm)](2)MCl(2)}(5+).

Bipyrimidine-bridged trimetallic complexes of the form {[(bpy)(2)Ru(bpm)](2)MCl(2)}(5+), where M = Rh(III) or Ir(III), bpy = 2,2'-bipyridine, and bpm = 2,2'-bipyrimidine, have been synthesized and characterized. These complexes are of interest in that they couple catalytically active rhodium(III) and iridium(III) metals with light-absorbing ruthenium(II) metals within a polymetallic framework. Their molecular composition is a light absorber-electron collector-light absorber core of a photochemical molecular device (PMD) for photoinitiated electron collection. The variation of the central metal has some profound effects on the observed properties of these complexes. The electrochemical data for the title trimetallics consist of a Ru(II/III) oxidation and sequential reductions assigned to the bipyrimidine ligands, Ir or Rh metal centers, and bipyridines. In both trimetallic complexes, the first oxidation is Ru based and the bridging ligand reductions occur prior to the central metal reduction. This illustrates that the highest occupied molecular orbital (HOMO) is localized on the ruthenium metal center and the lowest unoccupied molecular orbital resides on the bpm ligand. This bpm-based LUMO in {[(bpy)(2)Ru(bpm)](2)RhCl(2)}(5+) is in contrast with that observed for the monometallic [Rh(bpm)(2)Cl(2)](+) where the Rh(III)/Rh(I) reduction occurs prior to the bpm reduction. This orbital inversion is a result of bridge formation upon construction of the trimetallic complex. Both the Ir- and Rh-based trimetallic complexes exhibit a room temperature emission centered at 800 nm with tau = 10 ns. A detailed comparison of the spectroscopic, electrochemical, and spectroelectrochemical properties of these polymetallic complexes is described herein.

Electrochemical, Spectroscopic, and Spectroelectrochemical Properties of Synthetically Useful Supramolecular Light Absorbers with Mixed Polyazine Bridging Ligands.

The trimetallic complexes [{(bpy)(2)M(dpp)}(2)Ru(dpq)](6+) (M = Ru(II) or Os(II), bpy = 2,2'-bipyridine, dpp = 2,3-bis(2-pyridyl)pyrazine, and dpq = 2,3-bis(2-pyridyl)quinoxaline) have been prepared and the details of their spectroscopic, electrochemical, and spectroelectrochemical properties investigated. These mixed bridging ligand complexes are a new group of synthons that can be useful for the construction of supramolecular devices for a wide variety of functions. It is the presence of the terminal dpq ligand that allows for their incorporation into larger supramolecular systems. This dpq ligand serves as an acceptor ligand that will possess a lower lying pi orbital than the dpp ligands once these chromophores are incorporated into larger systems. The [{(bpy)(2)M(dpp)}(2)Ru(dpq)](6+) systems display overlapping terminal metal oxidations at 1.66 and 1.18 V vs Ag/AgCl for the Ru and Os systems, respectively. This indicates that within this framework, these terminal, M, metals are largely electronically uncoupled. No oxidative process for the central Ru metal center is observed within our solvent window. The [{(bpy)(2)M(dpp)}(2)Ru(dpq)](6+) systems have M --> dpp charge transfer (CT) lowest lying excited states. The [{(bpy)(2)Ru(dpp)}(2)Ru(dpq)](6+) Ru --> dpp CT state displays an emission centered at 775 nm with a lifetime of 65 ns at room temperature in deoxygenated CH(3)CN solution. The details of the electrochemical, spectroscopic, and spectroelectrochemical studies of these supramolecular light absorbers and the dichloro synthons, [{(bpy)(2)M(dpp)}(2)RuCl(2)](4+), are reported herein.

Choice-matching preference reversals in health outcome assessments.

BACKGROUND: Health outcome utility assessments generally assume procedural invariance. Preference reversals violating procedural invariance occur in economic scenarios when the assessment process shifts from a choice to a fill-in-the-blank task. PURPOSE: To determine if similar reversals occur in utility assessments. METHODS: One hundred thirty-six volunteer subjects completed 6 preference assessments of 4 personal health scenarios. Patients responded to otherwise identical tasks using either choice or fill-in-the-blank processes in a randomized crossover design. The authors determined the percentage of subjects preferring, or inferred to prefer, a given choice. RESULTS: Preference reversals occurred in all assessment scenarios. CONCLUSIONS: These preference reversals are a potential source of confusion for utility assessment and informed consent. They could be manipulated to achieve ends other than the best interest of patients. Anchoring or the prominence hypothesis may explain these findings.

Preference for fractures and other glucocorticoid-associated adverse effects among rheumatoid arthritis patients.

OBJECTIVE: The objective of this study was to determine rheumatoid arthritis (RA) patients' preferences for validated health state scenarios depicting glucocorticoid adverse events, predictors of these preferences, and psychometric properties of different preference techniques in this population. METHODS: Preferences were elicited by rating scale and time trade-off methods. Time trade-offs included trading current health for either time spent alive in an adverse health state for chronic conditions (time trade-off) or time spent in a sleeplike state for acute conditions (sleep trade-off). RESULTS: A total of 107 subjects with long-standing RA participated in the preference interviews. Mean preference values (rating scale/trade-off) were lowest for serious fracture adverse events, including hip fracture requiring a nursing home stay (0.55+/-0.22/0.76+/-0.36) and vertebral fracture with chronic pain (0.59+/-0.23/0.67+/-0.35), and highest for cataracts (0.84 + 0.17/0.96 0.09) and wrist fracture (0.82+/-0.18/0.81+/-0.29). Rating scales had a stronger correlation (r= 0.88) with physician ranking of scenarios than trade-off methods (r = 0.31). All methods were feasible and demonstrated good reliability, while rating scale method showed better construct validity than trade-off techniques. CONCLUSION: Relative to their current health, RA patients assigned low preference values to many glucocorticoid adverse events, particularly those associated with chronic fracture outcomes. Results varied with the preference measure used, indicating that methodological attributes of preference determinations must be considered in clinical decision making.

Population-based time preferences for future health outcomes.

CONTEXT: Time preference (how preference for an outcome changes depending on when the outcome occurs) affects clinical decisions, but little is known about determinants of time preferences in clinical settings. OBJECTIVES: To determine whether information about mean population time preferences for specific health states can be easily assessed, whether mean time preferences are constant across different diseases, and whether under certain circumstances substantial fractions of the patient population make choices that are consistent with a negative time preference. DESIGN: Self-administered survey. SETTING: Family physician waiting rooms in four states. PATIENTS: A convenience sample of 169 adults. INTERVENTION: Subjects were presented five clinical vignettes. For each vignette the subject chose between interventions maximizing a present and a future health outcome. The options for individual vignettes varied among the patients so that a distribution of responses was obtained across the population of patients. MAIN OUTCOME MEASURE: Logistic regression was used to estimate the mean preference for each vignette, which was translated into an implicit discount rate for this group of patients. RESULTS: There were marked differences in time preferences for future health outcomes based on the five vignettes, ranging from a negative to a high positive (116%) discount rate. CONCLUSIONS: The study provides empirical evidence that time preferences for future health outcomes may vary substantially among disease conditions. This is likely because the vignettes evoked different rationales for time preferences. Time preference is a critical element in patient decision making and cost-effectiveness research, and more work is necessary to improve our understanding of patient preferences for future health outcomes.

Estimating the health consequences of replacing cigarettes with nicotine inhalers.

BACKGROUND: A fast acting, clean nicotine delivery system might substantially displace cigarettes. Public health consequences would depend on the subsequent prevalence of nicotine use, hazards of delivery systems, and intrinsic hazards of nicotine. METHODS: A spreadsheet program, DEMANDS, estimates differences in expected mortality, adjusted for nicotine delivery system features and prevalence of nicotine use, by extending the data and methods of the SAMMEC 3 software from the US Centers for Disease Control and Prevention. The user estimates disease risks attributable to nicotine, other smoke components, and risk factors that coexist with smoking. The public health consequences of a widely used clean nicotine inhaler replacing cigarettes were compared to historical observations and public health goals, using four different risk attribution scenarios and nicotine use prevalence from 0-100%. MAIN OUTCOME MEASURES: Changes in years of potential life before age 85 (YPL85). RESULTS: If nicotine accounts for less than a third of smokers' excess risk of SAMMEC diseases, as it most likely does, then even with very widespread use of clean nicotine DEMANDS predicts public health gains, relative to current tobacco use. Public health benefits accruing from a widely used clean nicotine inhaler probably equal or exceed the benefits of achieving Healthy People 2010 goals. CONCLUSIONS: Clean nicotine inhalers might improve public health as much as any feasible tobacco control effort. Although the relevant risk estimates are somewhat uncertain, partial nicotine deregulation deserves consideration as part of a broad tobacco control policy.

Arterial infusion chemotherapy for palliation in far-advanced malignant neoplasms.

For patients with far-advanced regionally localized malignancies, arterial infusion chemotherapy offers reasonable palliation with minimal complications. High locoregional concentration of the antineoplastic drugs is obtained with relatively little systemic toxicity.

An evaluation of readable preventive health messages.

Distributing printed preventive health material has not been shown to change patient behavior. The lack of effect could be due to unreadable or boring materials. This could be corrected by choosing appropriate literature for each patient. A computer program was written to print booklets of relevant preventive health information matched by SMOG or Spache readability scores to a patient's self-reported educational level. The system was evaluated by printing booklets for 81 randomly selected new patients entering a family practice residency clinic setting, using the clinic's health history questionnaire to choose relevant preventive health information. After three months, patients showed no increase in obtaining flexible sigmoidoscopy, diphtheria-tetanus boosters, or cholesterol screens, when compared to 213 control patients. Use of readability matched materials in patient education efforts is logical, but was not sufficient to affect preventive health behavior in this study.