Head and neck radiotherapy quality assurance conference for dedicated review of delineated targets and organs at risk: results of a prospective study.

Purpose: Head and neck (HN) radiotherapy (RT) is complex, involving multiple target and organ at risk (OAR) structures delineated by the radiation oncologist. Site-agnostic peer review after RT plan completion is often inadequate for thorough review of these structures. In-depth review of RT contours is critical to maintain high-quality RT and optimal patient outcomes. Materials and Methods: In August 2020, the HN RT Quality Assurance Conference, a weekly teleconference that included at least one radiation oncology HN specialist, was activated at our institution. Targets and OARs were reviewed in detail prior to RT plan creation. A parallel implementation study recorded patient factors and outcomes of these reviews. A major change was any modification to the high-dose planning target volume (PTV) or the prescription dose/fractionation; a minor change was modification to the intermediate-dose PTV, low-dose PTV, or any OAR. We analysed the results of consecutive RT contour review in the first 20 months since its initiation. Results: A total of 208 patients treated by 8 providers were reviewed: 86·5% from the primary tertiary care hospital and 13·5% from regional practices. A major change was recommended in 14·4% and implemented in 25 of 30 cases (83·3%). A minor change was recommended in 17·3% and implemented in 32 of 36 cases (88·9%). A survey of participants found that all (n = 11) strongly agreed or agreed that the conference was useful. Conclusion: Dedicated review of RT targets/OARs with a HN subspecialist is associated with substantial rates of suggested and implemented modifications to the contours.

Patient assessment of lower urinary tract symptoms using the international prostate symptom score following low-dose-rate prostate brachytherapy.

PURPOSE: To correlate changes in urinary patient-reported outcomes including the International Prostate Symptom Score (IPSS), acute urinary retention and urethral stricture with urethral dose in those treated with low dose rate (LDR) prostate brachytherapy. MATERIALS AND METHODS: Patients treated with prostate LDR between 2012 and 2019 (n=117) completed IPSS urinary symptom assessments prior to treatment and at each follow-up. CT simulation was obtained with urinary catheter 1-month post-implant for dosimetric analysis. 113 patients with pre- and ≥1 post-LDR IPSS score available were analyzed. Urethral dosimetric parameters including U75, U100, U125, U150 and U200 were abstracted from post-implant dosimetry and assessed for association with urinary toxicity using bivariate logistic regression and Spearman correlation. Outcomes included clinically significant change (CSC, defined as 4 or more points or 25% rise above baseline) in IPSS score at 6 and 12 months, acute urinary retention (AUR), and urethral stricture (US). RESULTS: 89 (79%) patients were treated with LDR monotherapy (145 Gy) and 24 (21%) with LDR boost (110 Gy) with external beam radiation therapy. Twenty (18%) had baseline IPSS ≥15. Median IPSS scores were: baseline 6 (3-12; n=113), 1-month 17 (10-25; n=110), 6 months 12 (7-18; n=77), 1 year 8 (5-14; n=52). CSC-6 was observed in 59 (77%), CSC-12 in 26 (50%), AUR in 12 (11%), and US in 4 (4%). No association was identified between urethral dose parameters and CSC-6, CSC-12, AUR, or US. No correlation between urethral dose and IPSS at 6- and 12-months was identified. The IPSS ≥15 group exhibited lower rates of CSC-12 (13% v. 57%, p=0.05) but not CSC-6 (55% v. 80%, p=0.12). CONCLUSIONS: We did not find a relationship between urethral dose and IPSS elevation, AUR or US. We did identify a significantly lower change in IPSS at 12 months for those with baseline IPSS ≥15 compared to those with low baseline scores.

Roles of Grainyhead-like transcription factors in cancer.

The mammalian homologs of the D. melanogaster Grainyhead gene, Grainyhead-like 1-3 (GRHL1, GRHL2 and GRHL3), are transcription factors implicated in wound healing, tubulogenesis and cancer. Their induced target genes encode diverse epithelial cell adhesion molecules, while mesenchymal genes involved in cell migration and invasion are repressed. Moreover, GRHL2 suppresses the oncogenic epithelial-mesencyhmal transition, thereby acting as a tumor suppressor. Mechanisms, some involving established cancer-related signaling/transcription factor pathways (for example, Wnt, TGF-ß, mir200, ZEB1, OVOL2, p63 and p300) and translational implications of the Grainyhead proteins in cancer are discussed in this review article.

Effects of fluidized gas desulfurization (FGD) gypsum on non-target freshwater and sediment dwelling organisms.

Fluidized gas desulfurization gypsum is a popular agricultural soil amendment used to increase calcium and sulfur contents, and reduce aluminum toxicity. Due to its surface application in conservation tillage systems and high solubility, the soluble components of gypsum may be transferred with agricultural runoff into receiving waters. The current study measured toxicity of gypsum to Ceriodaphnia dubia, Pimephales promelas, Chironomus dilutus, and Hyalella azteca. Solutions at 2,400 mg gypsum/L (maximum solubility) produced no observable toxicity to C. dubia and P. promelas. Mixtures of a control sediment and gypsum indicated no observed toxicity effects for H. azteca, although effects were noted at 25% dilution for C. dilutus. Data suggest gypsum is not harmful to freshwater organisms at concentrations expected in the agricultural environment.

Considerations for assessments of wadable drainage systems in the agriculturally dominated deltas of Arkansas and Mississippi.

The watershed approach, currently used to assess regional streams in the United States, emphasizes least-disturbed reference conditions. Consideration of extensive wadable drainage systems found in Arkansas and Mississippi deltas challenges concepts of disturbance within a landscape of historic agricultural land use. Seventeen wadable drainage ditch sites in Arkansas and Mississippi deltas were characterized using water quality parameters and rapid bioassessment protocols. In all, 19 fish and 105 macroinvertebrate taxa were identified. Macroinvertebrate assemblages were dominated by coleopteran, dipteran, and hemipteran taxa at most drainage sites. Predominance of mobile, early colonists in ditches limits applicability of some metrics for assessment of stream integrity beyond prevalent conditions of ephemeral water quantity and habitat maintenance. This study provides evidence of considerable variability of physical characteristics, water quality, and fish and invertebrate metrics in wadable drainage systems. It indicates a disparity in usefulness of the watershed approach, emphasizing least-disturbed reference conditions, in assessing ecological integrity for a region with ditches as dominant landscape features.

Assessing caffeine as an emerging environmental concern using conventional approaches.

Organic wastewater contaminants, including pharmaceuticals, caffeine, and nicotine, have received increased scrutiny because of their detection in water bodies receiving wastewater discharge. Despite recent measurement in United States streams, caffeine's effect on freshwater organisms is not well documented. The present study measured caffeine's lethal and sublethal effects on the freshwater species, Ceriodaphnia dubia, Pimephales promelas, and Chironomus dilutus. These organisms, which are used in standard testing or effluent monitoring, were exposed to aqueous caffeine solutions under static exposure for 48 hours and daily renewed static exposure for 7 days. Averaged responses of 48-hour acute end points indicated that C. dubia was more sensitive to caffeine exposures (LC50 = 60 mg/L) than either P. promelas (LC50 = 100 mg/L) or C. dilutus (LC50 = 1,230 mg/L). Exposure-response slopes confirmed these findings (3% mortality/mg/L for C. dubia; 0.5% mortality/mg/L for P. promelas; and 0.07% mortality/mg/L for C. dilutus). Comparative 7-day responses between C. dubia and P. promelas (LC50 = 46 and 55 mg/L, respectively) were more similar than the broad range of acute values. Sublethal effects measured for caffeine exposure included impaired C. dubia reproduction (IC50 = 44 mg/L) and inhibited P. promelas growth (IC50 = 71 mg/L). According to the results of this study, combined with earlier studies reporting environmental concentrations and product half-lives, caffeine should pose negligible risk for most aquatic vertebrate and invertebrate organisms.

Assessment of diazinon toxicity in sediment and water of constructed wetlands using deployed Corbicula fluminea and laboratory testing.

Constructed wetlands for mitigation of nonpoint agricultural runoff have been assessed for their ability to decrease potential toxicity from associated contaminants. After a simulated runoff event, constructed wetlands positioned in series were used to measure the effects of the organophosphate insecticide diazinon. Water, sediment, and plant samples from five sites were analyzed for diazinon concentrations from 0.5 hours to 26 days; peak concentrations were measured in sediment after 0.5 hours (268.7 microg/kg) and in water and plant tissue after 3 hours (121.71 microg/L and 300.7 microg/kg, respectively). Cholinesterase activity and changes in shell growth were measured from Corbicula fluminea deployed at corresponding sites. Water collected after 9 hours from all wetland sites contained diazinon concentrations sufficient to cause toxicity to Ceriodaphnia dubia, but not to Pimephales promelas. C. dubia survival was decreased in water sampled through 7 days from the site nearest runoff introduction, whereas C. fluminea deployed at this same site experienced 100% mortality after 26 days. Clams from lower sites survived wetland conditions, but growth and ChE activity were significantly decreased lower than that of clams from a control site. C. dubia exposed to water from these sites continued to have decreased survival throughout the 26-day sampling. Sediment sampled from 48 hours through 14 days at the lowest wetland site decreased the laboratory survival of Chironomus dilutus, and sediment from upper sites elicited an effect only on day 26. Although wetland concentrations of aqueous diazinon were decreased lower than toxic thresholds after 26 days, decreased ChE activity in deployed clams provided evidence of residual diazinon effects to deployed organisms.

Hydroponic uptake of atrazine and lambda-cyhalothrin in Juncus effusus and Ludwigia peploides.

Phytoremediation encompasses an array of plant-associated processes known to mitigate contaminants from soil, sediment, and water. Modification of pesticides associated with agricultural runoff includes processes directly associated with aquatic macrophytes in addition to changes in soil geochemistry and associated rhizospheric degradation. Remediation attributes of two vegetative species common to agricultural drainages in the Mississippi Delta, USA, were assessed using atrazine and lambda-cyhalothrin. Concentrations used in 8-d hydroponic exposures were calculated using recommended field applications and a 5% runoff model from a 0.65-cm rainfall event on a 2.02-ha field. While greater atrazine uptake was measured in Juncus effusus, greater lambda-cyhalothrin uptake occurred in Ludwigia peploides. Maximum pesticide uptake was reached within 48h for each exposure and subsequent translocation of pesticides to upper plant biomass occurred in macrophytes exposed to atrazine. Sequestration of 98.2% of lambda-cyhalothrin in roots of L. peploides was measured after 8d. Translocation of lambda-cyhalothrin in J. effusus resulted in 25.4% of pesticide uptake partitioned to upper plant biomass. These individual macrophyte remediation studies measured species- and pesticide-specific uptake rates, indicating that seasonality of pesticide applications and macrophyte emergence might interact strongly to enhance mitigation capabilities in edge-of-field conveyance structures.

Evaluation of aquatic toxicities of chromium and chromium-containing effluents in reference to chromium electroplating industries.

This study evaluated aquatic toxicities of chromium and chromium-containing laboratory samples representative of effluents from chromium electroplating industries, and compared the aquatic environmental risks of hexavalent and trivalent chromium electroplating operations. Trivalent chromium electroplating has emerged as an acceptable alternative to hazardous hexavalent chromium electroplating. This process substitution has reduced the human health impact in the workplace and minimized the production of hazardous sludge regulated under the Resource Conservation and Recovery Act (RCRA). The thrust behind this research was to investigate whether trivalent chromium electroplating operations have lower adverse impacts on standardized toxicity test organisms. Ceriodaphnia dubia and Pimephales promelas were used to investigate toxicities of trivalent chromium (Cr (III)), hexavalent chromium (Cr (VI)), and industrial effluents. In agreement with previous studies, Cr (III) was found to be less toxic than Cr (VI). Despite having several organic and inorganic constituents in the effluents obtained from trivalent chromium plating baths, they exhibited less adverse effects to C. dubia than effluents obtained from hexavalent chromium electroplating baths. Thus, transition from hexavalent to trivalent chromium electroplating processes may be justified. However, because of the presence of organic constituents such as formate, oxalate, and triethylene glycol in effluents, trivalent chromium electroplating operations may face additional regulatory requirements for removal of total organic carbon.

Influence of vegetation in mitigation of methyl parathion runoff.

A pesticide runoff event was simulated on two 10 m x 50 m constructed wetlands (one non-vegetated, one vegetated) to evaluate the fate of methyl parathion (MeP) (Penncap-M). Water, sediment, and plant samples were collected at five sites downstream of the inflow for 120 d. Semi-permeable membrane devices (SPMDs) were deployed at each wetland outflow to determine exiting pesticide load. MeP was detected in water at all locations of the non-vegetated wetland (50 m), 30 min post-exposure. MeP was detected 20 m from the vegetated wetland inflow 30 min post-exposure, while after 10d it was detected only at 10 m. MeP was measured only in SPMDs deployed in non-vegetated wetland cells, suggesting detectable levels were not present near the vegetated wetland outflow. Furthermore, mass balance calculations indicated vegetated wetlands were more effective in reducing aqueous loadings of MeP introduced into the wetland systems. This demonstrates the importance of vegetation as sorption sites for pesticides in constructed wetlands.

Community-level physiological profiles of cloacal microbes in songbirds (order: Passeriformes): variation due to host species, host diet, and habitat.

The relationship between microorganisms and birds has received increased attention recently. The state of knowledge of this relationship, however, is based largely on examination of sick or dead birds, and knowledge of the prevalence and community structure and function of microbes in healthy wild populations is limited. Using carbon substrate utilization profiles, microbial communities were examined in 91 cloacal samples from 14 species within apparently healthy summer and winter passerine populations. Within each season, gradient lengths and eigenvalues from ordination analyses suggested that many samples differed in their carbon substrate utilization and several had very different communities. Cloacal microbe carbon utilization profiles were distinguishable among host species, season-specific diet, and study site in the ordination analyses. However, these patterns were only observed for the analysis of the summer data set. The results of this study support the idea that the avian host's microbial community, relative to carbon substrate utilization, is related to host diet. Previously, this pattern had only been reported for potential pathogens isolated from the avian cloaca. Study site-specific patterns in the ordination analysis suggest that environmental conditions at a particular study site may influence cloacal microbial communities in birds. Results of this study indicate that examination of community-level physiological profiles may be a useful technique for distinguishing among avian cloacal samples, similar to that already established for discriminating aqueous and soil samples. Future studies that correlate microbe physiological profiles to condition-based indices of avian hosts may be most useful for eventually using the profile as an indicator of environmental conditions experienced by hosts.

Evaluated fate and effects of atrazine and lambda-cyhalothrin in vegetated and unvegetated microcosms.

Contaminants such as nutrients, metals, and pesticides can interact with constructed wetlands and existing drainage ditches used as agricultural best-management practices. Our research has shown that the presence of macrophytes and a hydrologic regime aid in the transfer and transformation of pesticides associated with agricultural runoff. This study consisted of application of both atrazine (triazine herbicide) and lambda-cyhalothrin (pyrethroid insecticide) to vegetated and unvegetated microcosms in order to measure the fate and effects of pesticides applied at suggested field application rates. Exposures focused on monocultures of Ludwigia peploides (water primrose) and Juncus effusus (soft rush). Pesticide sorption was evident through concentrations of atrazine and lambda-cyhalothrin in plant tissue as high as 2461.4 and 86.50 microg/kg, respectively. Toxicity was measured in water from unvegetated microcosms for 28 days and in Chironomus tentans (midge larvae) exposed to sediment collected from 3 h to 56 days in microcosms receiving the pesticide combination. The comparative survival of test organisms in this study suggests that effective mitigation of pesticides from runoff can depend on the macrophyte contact and vegetative attributes associated with ditches.

Acute toxicity of six freshwater mussel species (Glochidia) to six chemicals: implications for Daphnids and Utterbackia imbecillis as surrogates for protection of freshwater mussels (Unionidae).

Acute (24-h) toxicity tests were used in this study to compare lethality responses in early life stages (glochidia) of six freshwater mussel species, Leptodea fragilis, U. imbecillis, Lampsilis cardium, Lampsilis siliquoidea, Megalonaias nervosa, and Ligumia subrostrata, and two standard test organisms, Ceriodaphnia dubia and Daphnia magna. Concentrations of carbaryl, copper, 4-nonylphenol, pentachlorophenol, permethrin, and 2,4-D were used in acute exposures to represent different chemical classes and modes of action. The relative sensitivities of species were evaluated by ranking their LC50 values for each chemical. We used these ranks to determine the extent to which U. imbecillis (one of the most commonly used unionids in toxicity tests) was representative of the tolerances of other mussels. We also calculated geometric mean LC50s for the families Unionidae and Daphnidae. Rankings of these data were used to assess the extent to which Daphnidae can be used as surrogates for freshwater mussels relative to chemical sensitivity. While no single chemical elicited consistently high or low toxicity estimates, carbaryl and 2,4-D were generally the least toxic to all species tested. No species was always the most sensitive, and Daphnidae were generally protective of Unionidae. Utterbackia imbecillis, while often proposed as a standard unionid mussel test species, did not always qualify as a sufficient surrogate (i.e., a substitute organism that often elicits similar sensitivity responses to the same contaminant exposure) for other species of mussels, since it was usually one of the more tolerant species in our rankings. U. imbecillis should be used as a surrogate species only with this caution on its relative insensitivity.

Evaluating acute toxicity of methyl parathion application in constructed wetland mesocosms.

Wetland ecosystems have reduced ambient levels of various organic and metallic compounds, although their effectiveness on agricultural pesticides is not well documented. Five stations within each of two 10 x 50 m constructed wetlands (two vegetated, two nonvegetated) were selected to measure the fate and effects of methyl parathion (MeP). Following a simulated storm event (0.64 cm of rainfall), aqueous, sediment, and plant samples were collected and analyzed spatially (5, 10, 20, and 40 m from the inlet) and temporally (after 3-10 days) for MeP concentrations and for the impact of those concentrations on the aquatic fauna. Aqueous toxicity to fish decreased spatially and temporally in the vegetated mesocosm. Pimephales promelas survival was significantly reduced, to 68%, at the 10-m station of the nonvegetated wetlands (3 h postapplication), with pesticide concentrations averaging 9.6 microg MeP/L. Ceriodaphnia in both the vegetated and nonvegetated wetlands was sensitive (i.e., a significant acute response to MeP occurred) to pesticide concentrations through 10 days postapplication. Mean MeP concentrations in water ranged from 0.5 to 15.4 microg/L and from 0.1 to 27.0 microg/L in the vegetated and nonvegetated wetlands, respectively. Hyalella azteca aqueous tests resulted in significant mortality in the 5-m vegetated segment 10 days after exposure to MeP (2.2 microg/L). Solid-phase (10-day) sediment toxicity tests showed no significant reduction in Chironomus tentans survival or growth, except for the sediments sampled 3 h postapplication in the nonvegetated wetland (65% survival). Thereafter, midge survival averaged >87% in sediments sampled from both wetlands. These data suggest that wetlands play a significant role in mitigating the effect of MeP exposure in sensitive aquatic biota.

Vegetative and structural characteristics of agricultural drainages in the Mississippi Delta landscapes.

Agricultural drainage ditches in the Mississippi Alluvial Delta landscape vary from edge-of-field waterways to sizeable drainages. Ditch attributes vary with size, location and maintenance and may aid in mitigation of contaminants from agricultural fields. The goal of this study was to better understand how vegetative characteristics affect water quality in conveyance structures in the context of ditch class and surrounding land use. Characterization of 36 agricultural ditches included presence of riparian buffer strips, water depth, surrounding land use, vegetative cover, and associated aqueous physicochemical parameters. Vegetation was assessed quantitatively, obtaining stem counts in a sub-sample of ditch sites, using random quadrat method. Physical features varied with ditch size and vegetative diversity was higher in larger structures. Polygonum sp. was the dominant bed vegetation and was ubiquitous among site sizes. Macrophytes varied from aquatic to upland species, and included Leersia sp. and upland grasses (Poaceae family) in all drainage size classes. Percent cover of bed and bank varied from 0 to 100% and 70 to 100%, respectively, and highest nutrient values were measured in sites with no buffer strips. These conveyance structures and surrounding buffer zones are being ranked for their ability to reduce excess nutrients, suspended solids, and pesticides associated with runoff.

Evaluating toxicity of Asana XL (esfenvalerate) amendments in agricultural ditch mesocosms.

Agricultural ditches primarily serve to remove and store excess water associated with irrigation and storm events. The ability of these ecosystems to mitigate potential contaminants is not well understood. Five sites along a 650-m agricultural ditch located in the Mississippi Delta Management Systems Evaluation Area (MDMSEA) were used to measure fate and effects of an esfenvalerate (insecticide) exposure. Following a 0.64-cm simulated storm event, samples were collected from water and sediments and analyzed spatially from five sites and temporally from 0.5 h to 56 d. Results of aqueous toxicity bioassays indicated that lethality progressed downstream throughout all sampling intervals, while sediment toxicity bioassays only elicited biological responses at the point of pesticide application to the ditch (0 m). Significant reductions in survival of Ceriodaphnia dubia and Pimephales promelas in water were measured at the 0-, 20-, and 80-m sites following application. Ten-day solid phase sediment testing of Chironomus tentans indicated persistent toxicity only at the point of application (0 m) and throughout 56 d (mean=14.4% survival). No lethality or significant reduction in midge growth was measured for remaining downstream sites. These measurements were used to evaluate the potential of agricultural ditches to reduce potential deleterious effects of contaminants in agricultural drainage systems that precede receiving streams.

Innovative uses of vegetated drainage ditches for reducing agricultural runoff.

Vegetated agricultural ditches play an important role in mitigation of pesticides following irrigation and storm runoff events. In a simulated runoff event in the Mississippi (USA) Delta, the mitigation capacity of a drainage ditch using the pyrethroid esfenvalerate (Asana XL) was evaluated. The pesticide was amended to soil prior to the runoff event to simulate actual runoff, ensuring the presence of esfenvalerate in both water and suspended particulate phases. Water, sediment, and plant samples were collected temporally and spatially along the drainage ditch. Even with mixing of the pesticide with soil before application, approximately 99% of measured esfenvalerate was associated with ditch vegetation (Ludwigia peploides, Polygonum amphibium, and Leersia oryzoides) three hours following event initiation. This trend continued for the 112 d study duration. Simple modeling results also suggest that aqueous concentrations of esfenvalerate could be mitigated to 0.1% of the initial exposure concentration within 510 m of a vegetated ditch. Observed field half-lives in water, sediment, and plant were 0.12 d, 9 d, and 1.3 d, respectively. These results validate the role vegetation plays in the mitigation of pesticides, and that ditches are an indispensable component of the agricultural production landscape.

Acute toxicity of methyl-parathion in wetland mesocosms: assessing the influence of aquatic plants using laboratory testing with Hyalella azteca.

Methyl-parathion (MeP) was introduced into constructed wetlands for the purpose of assessing the importance of distance from the source of contamination and the role of emergent vegetation on the acute toxicity to Hyalella azteca (Crustacea: Amphipoda). A vegetated (90% cover: mainly Juncus effuses) and a nonvegetated wetland (each with a water body of 50 x 5.5 x 0.2 m) were each exposed to a simulated MeP storm runoff event. H. azteca was exposed for 48 h in the laboratory to water samples taken from the wetlands at a distance of 5, 10, 20, and 40 m from the pesticide inlet 3 h, 24 h, 96 h, and 10 days following application. Methyl-parathion was detected throughout the nonvegetated wetland, whereas the pesticide was only transported halfway through the vegetated wetland. A repeated-measure three-way analysis of variance (ANOVA) using time, location, and vegetation indicated significantly lower toxicity in the vegetated wetland. Furthermore, the mortality decreased significantly with both increasing distance from the inlet and time (48-h LC50 +/- 95% CI: 9.0 +/- 0.3 microg/L). A significant three-way interaction of time x vegetation x location confirmed higher toxicity at the inlet area of the nonvegetated wetland immediately after contamination. Significant linear regressions of maximum mortality (independent of time) versus distance from the pesticide inlet indicated that 44 m of vegetated and 111 m of nonvegetated wetland would reduce H. azteca mortality to < or = 5%. These results suggest that vegetation contributes to reduced MeP effects in constructed wetlands.

Factors affecting the usefulness of impenetrable interface element borders.

N. Walker and J. B. Smelcer (1990) found that selection times for menus could be reduced by placing the menus adjacent to the edge of the screen; this creates a border between the menu and the edge of the screen that the mouse cursor cannot penetrate. Based on this finding, they proposed that selection times for graphical user interface targets could be reduced by employing these impenetrable borders. Four studies tested this prediction with a Web browser's back button and scroll bar. Results demonstrated that targets employing impenetrable borders were always selected faster than were targets placed 1 pixel from the edge of the screen, which supports Walker and Smelcer's prediction. However, within the constraints of the current studies, this speed advantage asymptotes at approximately 283 ms for target heights of 2.00 cm and target distances of 3.50 cm. In addition, these findings generalized across most angles of approach. Actual or potential applications of this research include target placement decisions in the design or modification of graphical user interfaces.