SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID-19: The International Study of Inflammation in COVID-19.

Severe coronavirus disease 2019 (COVID-19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID-19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID-19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, interleukin-6, procalcitonin, ferritin, and D-dimer. In-hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL-6 (0.614), D-dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%-98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%-96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%-96.7%) and NPV of 95.5% (93.1%-97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low-risk patients with COVID-19.

Low- or high-white light irradiance induces similar conidial stress tolerance in Metarhizium robertsii.

White light during mycelial growth influences high conidial stress tolerance of the insect-pathogenic fungus Metarhizium robertsii, but little is known if low- or high-white light irradiances induce different stress tolerances. The fungus was grown either in the dark using two culture media: on minimal medium (Czapek medium without sucrose = MM) or on potato dextrose agar (PDA) or PDA medium under five different continuous white light irradiances. The stress tolerances of conidia produced on all treatments were evaluated by conidial germination on PDA supplemented with KCl for osmotic stress or on PDA supplemented with menadione for oxidative stress. Conidia produced on MM in the dark were more tolerant to osmotic and oxidative stress than conidia produced on PDA in the dark or under the light. For osmotic stress, growth under the lower to higher irradiances produced conidia with similar tolerances but more tolerant than conidia produced in the dark. For oxidative stress, conidia produced under the white light irradiances were generally more tolerant to menadione than conidia produced in the dark. Moreover, conidia produced in the dark germinated at the same speed when incubated in the dark or under lower irradiance treatment. However, at higher irradiance, conidial germination was delayed compared to germination in the dark, which germinated faster. Therefore, growth under light from low to high irradiances induces similar conidial higher stress tolerances; however, higher white light irradiances cause a delay in germination speed.

Virulence of the insect-pathogenic fungi Metarhizium spp. to Mormon crickets, Anabrus simplex (Orthoptera: Tettigoniidae).

The Mormon cricket (MC), Anabrus simplex Haldeman, 1852 (Orthoptera: Tettigoniidae), has a long and negative history with agriculture in Utah and other western states of the USA. Most A. simplex populations migrate in large groups, and their feeding can cause significant damage to forage plants and cultivated crops. Chemical pesticides are often applied, but some settings (e.g. habitats of threatened and endangered species) call for non-chemical control measures. Studies in Africa, South America, and Australia have assessed certain isolates of Metarhizium acridum as very promising pathogens for Orthoptera: Acrididae (locust) biocontrol. In the current study, two isolates of Metarhizium robertsii, one isolate of Metarhizium brunneum, one isolate of Metarhizium guizhouense, and three isolates of M. acridum were tested for infectivity to MC nymphs and adults of either sex. Based on the speed of mortality, M. robertsii (ARSEF 23 and ARSEF 2575) and M. brunneum (ARSEF 7711) were the most virulent to instars 2 to 5 MC nymphs. M. guizhouense (ARSEF 7847) from Arizona was intermediate and the M. acridum isolates (ARSEF 324, 3341, and 3609) were the slowest killers. ARSEF 2575 was also the most virulent to instar 6 and 7 nymphs and adults of MC. All of the isolates at the conidial concentration of 1 × 107 conidia ml-1 induced approximately 100% mortality by 6 days post application of fungal conidia. In conclusion, isolates ARSEF 23, ARSEF 2575, and ARSEF 7711 acted most rapidly to kill MC under laboratory conditions. The M. acridum isolates, however, have much higher tolerance to heat and UV-B radiation, which may be critical to their successful use in field application.

UV-B tolerances of conidia, blastospores, and microsclerotia of Metarhizium spp. entomopathogenic fungi.

The aim of the present study was to analyze ten native Metarhizium spp. isolates as to their UV-B tolerances. Comparisons included: different fungal propagules (conidia, blastospores, or microsclerotia [MS]); conidia in aqueous suspensions or in 10% mineral oil-in-water emulsions; and conidia mixed with different types of soil. The UV-B effect was expressed as the germination of conidia or culturability of blastospores and MS relative to nongerminated propagules. Metarhizium anisopliae LCM S05 exhibited high tolerance as blastospores and/or MS, but not as conidia; LCM S10 and LCM S08 had positive results with MS or conidia but not blastospores. The formulations with 10% mineral oil did not always protect Metarhizium conidia against UV-B. Conidia of LCM S07, LCM S08, and LCM S10 exhibited the best results when in aqueous suspensions, 24 h after UV-B exposure. In general, conidia mixed with soil and exposed to UV-B yielded similar number of colony forming units as conidia from unexposed soil, regardless the soil type. It was not possible to predict which type of propagule would be the most UV-B tolerant for each fungal isolate; in conclusion, many formulations and propagule types should be investigated early in the development of new fungal biocontrol products.

Possible source of the high UV-B and heat tolerance of Metarhizium acridum (isolate ARSEF 324).

The isolate ARSEF 324 of Metarhizium acridum is very tolerant to UV-B radiation and heat, but the intrinsic traits behind the extreme tolerance of this isolate to both stress conditions have not been elucidated. Because trehalose and mannitol are documented stress reducers in fungi, we investigated the accumulation of these compounds in conidia of ARSEF 324 compared with the accumulation of these two compounds in conidia of M. robertsii (ARSEF 23 and ARSEF 2575), which are considerably more susceptible to UV-B radiation and heat than ARSEF 324. Conidia of ARSEF 324 produced on potato dextrose agar plus yeast extract accumulated two-fold more trehalose and mannitol than conidia of ARSEF 23 and ARSEF 2575 produced on the same medium. The high accumulation of trehalose and mannitol in conidia of ARSEF 324 suggests one mechanism that it uses to attain its high tolerance to UV-B radiation and heat.

Effect of heat stress and oil formulation on conidial germination of Metarhizium anisopliae s.s. on tick cuticle and artificial medium.

The effect of heat stress (45°C) versus non-heat stress (27°C) on germination of Metarhizium anisopliae sensu stricto (s.s.) isolate IP 119 was examined with conidia formulated (suspended) in pure mineral oil or in water (Tween 80, 0.01%), and then applied onto the cuticle of Rhipicephalus sanguineus sensu lato (s.l.) engorged females or onto culture medium (PDAY). In addition, bioassays were performed to investigate the effect of conidia heated while formulated in oil, then applied to blood-engorged adult R. sanguineus females. Conidia suspended in water then exposed to 45°C, in comparison to conidia formulated in mineral oil and exposed to the same temperature, germinated less and more slowly when incubated on either PDAY medium or tick cuticle. Also, conidial germination on tick cuticle was delayed in comparison to germination on artificial culture medium; for example, germination was 13% on tick cuticle 72h after inoculation, in contrast to 61.5% on PDAY medium. Unheated (27°C) conidia suspended in either water or oil and applied to tick cuticle developed appressoria 36h after treatment; whereas only heat-stressed conidia formulated in oil developed appressoria on tick cuticle. In comparison to conidia heated in mineral oil, there was a strong negative effect of heat on germination of conidia heated in water before being applied to arthropod cuticle. Nevertheless, bioassays [based primarily on egg production (quantity) and egg hatchability] exhibited high percentages of tick control regardless of the type of conidial suspension; i.e., water- or oil-formulated conidia, and whether or not conidia were previously exposed to heat. In comparison to aqueous conidial preparations, however, conidia formulated in oil reduced egg hatchability irrespective of heat or no-heat exposure. In conclusion, mineral-oil formulation protected conidia against heat-induced delay of both germination and appressorium production when applied to the cuticle of R. sanguineus.

Revisiting fetal dose during radiation therapy: evaluating treatment techniques and a custom shield.

To create a comprehensive dataset of peripheral dose (PD) measurements from a new generation of linear accelerators with and without the presence of a newly designed fetal shield, PD measurements were performed to evaluate the effects of depth, field size, distance from the field edge, collimator angle, and beam modi-fiers for common treatment protocols and modalities. A custom fetal lead shield was designed and made for our department that allows external beam treatments from multiple angles while minimizing the need to adjust the shield during patient treatments. PD measurements were acquired for a comprehensive series of static fields on a stack of Solid Water. Additionally, PDs from various clinically relevant treatment scenarios for pregnant patients were measured using an anthropomorphic phantom that was abutted to a stack of Solid Water. As expected, the PD decreased as the distance from the field edge increased and the field size decreased. On aver-age, a PD reduction was observed when a 90° collimator rotation was applied and/or when the tertiary MLCs and jaws defined the field aperture. However, the effect of the collimator rotation (90° versus 0°) in PD reduction was not found to be clini-cally significant when the tertiary MLCs were used to define the field aperture. In the presence of both the MLCs and the fetal shield, the PD was reduced by 58% at a distance of 10 cm from the field edge. The newly designed fetal shield may effectively reduce fetal dose and is relatively easy to setup. Due to its design, we are able to use a broad range of treatment techniques and beam angles. We believe the acquired comprehensive PD dataset collected with and without the fetal shield will be useful for treatment teams to estimate fetal dose and help guide decisions on treat-ment techniques without the need to perform pretreatment phantom measurements.

Combination esthetic treatment of anterior teeth affected by idiopathic enamel hypoplasia: a case report.

The esthetic management of enamel dysplasia presents an opportunity for the practitioner to integrate expertise in diagnosis, biomaterials, and technique. In addition to considerations of appearance, careful attention must be paid to occlusal function and restorative material properties. This case report highlights a combined approach of conservative lithium disilicate indirect restorations and composite resin direct veneers to electively restore the anterior teeth of a patient diagnosed with idiopathic enamel hypoplasia.

Molecular and physiological effects of environmental UV radiation on fungal conidia.

Conidia are specialized structures produced at the end of the asexual life cycle of most filamentous fungi. They are responsible for fungal dispersal and environmental persistence. In pathogenic species, they are also involved in host recognition and infection. Conidial production, survival, dispersal, germination, pathogenicity and virulence can be strongly influenced by exposure to solar radiation, although its effects are diverse and often species dependent. UV radiation is the most harmful and mutagenic waveband of the solar spectrum. Direct exposure to solar radiation for a few hours can kill conidia of most fungal species. Conidia are killed both by solar UV-A and UV-B radiation. In addition to killing conidia, which limits the size of the fungal population and its dispersion, exposures to sublethal doses of UV radiation can reduce conidial germination speed and virulence. The focus of this review is to provide an overview of the effects of solar radiation on conidia and on the major systems involved in protection from and repair of damage induced by solar UV radiation. The efforts that have been made to obtain strains of fungi of interest such as entomopathogens more tolerant to solar radiation will also be reviewed.

Tolerance of entomopathogenic fungi to ultraviolet radiation: a review on screening of strains and their formulation.

Ultraviolet radiation from sunlight is probably the most detrimental environmental factor affecting the viability of entomopathogenic fungi applied to solar-exposed sites (e.g., leaves) for pest control. Most entomopathogenic fungi are sensitive to UV radiation, but there is great inter- and intraspecies variability in susceptibility to UV. This variability may reflect natural adaptations of isolates to their different environmental conditions. Selecting strains with outstanding natural tolerance to UV is considered as an important step to identify promising biological control agents. However, reports on tolerance among the isolates used to date must be analyzed carefully due to considerable variations in the methods used to garner the data. The current review presents tables listing many studies in which different methods were applied to check natural and enhanced tolerance to UV stress of numerous entomopathogenic fungi, including several well-known isolates of these fungi. The assessment of UV tolerance is usually conducted with conidia using dose-response methods, wherein the UV dose is calculated simply by multiplying the total irradiance by the period (time) of exposure. Although irradiation from lamps seldom presents an environmentally realistic spectral distribution, laboratory tests circumvent the uncontrollable circumstances associated with field assays. Most attempts to increase field persistence of microbial agents have included formulating conidia with UV protectants; however, in many cases, field efficacy of formulated fungi is still not fully adequate for dependable pest control.

Stress tolerance and virulence of insect-pathogenic fungi are determined by environmental conditions during conidial formation.

The virulence to insects and tolerance to heat and UV-B radiation of conidia of entomopathogenic fungi are greatly influenced by physical, chemical, and nutritional conditions during mycelial growth. This is evidenced, for example, by the stress phenotypes of Metarhizium robertsii produced on various substrates. Conidia from minimal medium (Czapek's medium without sucrose), complex medium, and insect (Lepidoptera and Coleoptera) cadavers had high, moderate, and poor tolerance to UV-B radiation, respectively. Furthermore, conidia from minimal medium germinated faster and had increased heat tolerance and were more virulent to insects than those from complex medium. Low water-activity or alkaline culture conditions also resulted in production of conidia with high tolerance to heat or UV-B radiation. Conidia produced on complex media exhibited lower stress tolerance, whereas those from complex media supplemented with NaCl or KCl (to reduce water activity) were more tolerant to heat and UV-B than those from the unmodified complex medium. Osmotic and nutritive stresses resulted in production of conidia with a robust stress phenotype, but also were associated with low conidial yield. Physical conditions such as growth under illumination, hypoxic conditions, and heat shock before conidial production also induced both higher UV-B and heat tolerance; but conidial production was not decreased. In conclusion, physical and chemical parameters, as well as nutrition source, can induce great variability in conidial tolerance to stress for entomopathogenic fungi. Implications are discussed in relation to the ecology of entomopathogenic fungi in the field, and to their use for biological control. This review will cover recent technologies on improving stress tolerance of entomopathogenic fungi for biological control of insects.

The influence of conidial Pr1 protease on pathogenicity potential of Metarhizium anisopliae senso latu to ticks.

Pr1 is a subtilisin-like protease produced by Metarhizium spp. entomopathogenic fungi, and it is recognized as heavily involved in the initial steps of the fungal invasion of arthropod-host cuticles. In the current study, correlation was sought between mortality of tick larvae and conidial Pr1 levels of one Metarhizium anisopliae senso latu (s.l.) isolate (CG 148). Conidia with different levels of pr1 gene expression and enzymatic activity were obtained by producing them on either artificial medium (to yield low Pr1 activity) or on Rhipicephalus microplus cadavers (to yield high Pr1 activity). Conidial proteolytic activity was assessed using N-suc-ala-ala-pro-phe-ρNA as the chromogenic substrate, and pr1 expression was profiled by qPCR using three genes (gpd, try, and tef) as reference genes. Pr1 enzymatic (proteolytic) activity on conidia obtained from tick cadavers was 36 U mg(-1) in comparison to 4 U mg(-1) on conidia from PDA medium. Also, pr1 gene expression level was ten times higher in conidia from tick cadavers compared to PDA medium. Bioassays of M. anisopliae s.l. CG 148 spores with elevated Pr1 proteolytic activity and gene expression levels did not demonstrate increased virulence (= significant change percent mortality of tick larvae). The minimal levels of Pr1 on conidia produced on artificial medium was adequate to afford high levels of virulence, and the elevated amounts of the enzyme on tick-cadaver-produced conidia did not induce elevated larval mortality. As long as some Pr1 activity was present, fungal virulence of isolate CG 148 against tick larvae was not elevated by increased levels of conidial Pr1.

Selective patellar resurfacing in total knee arthroplasty: a prospective, randomized, double-blind study.

350 knees were evaluated in a prospective, randomized, double-blinded study of selective patellar resurfacing in primary total knee arthroplasty. Knees with exposed bone on the patellar articular surface were excluded. 327 knees were evaluated at a mean follow-up of 7.8years. 114 knees followed for greater than 10 years were analyzed separately. Satisfaction was higher in patients with a resurfaced patella. In patients followed for at least 10 years, no significant difference was found. No difference was found in KSS scores or survivorship. No complications of patellar resurfacing were identified. The vast majority of patients with remaining patellar articular cartilage do very well with total knee arthroplasty regardless of patellar resurfacing. Patient satisfaction may be slightly higher with patellar resurfacing.

Response to: Bouwman, H. et al. Hallogenated pollutants in terrestrial and aquatic bird eggs: converging patterns of pollutant profiles, and impacts and risks from higher levels Environ. Res. (2013) http://dx.doi.org/10.1016/j.envres.2013.06.003.

Bouwman and coauthors present data and analyses of DDT and other halogenated pollutants in environmental samples and based on their data and analyses thereof, argue against the use of DDT for malaria control. Regrettably, the analyses, presentations, and interpretations of data presented by Bouwman and coauthors are biased and erroneous.

Heat-induced post-stress growth delay: a biological trait of many Metarhizium isolates reducing biocontrol efficacy?

The habitats of many pest insects have fluctuating climatic conditions. To function effectively, the pathogens of these pests must be capable of infecting and developing disease at a wide range of temperatures. The current study examines ten Metarhizium spp. isolates as to their ability to recover normal metabolic activity after exposure to high temperature for several hours daily; and whether such recovery, with at least some isolates, requires a temporary repair ("retooling") period. Fungal colonies were exposed to 40°C for 4h or 8h followed by 20h or 16h at 28°C, respectively, for three consecutive days. Growth rates during treatments were compared to control plates (constant 28°C) and to plates with growth stoppage by cold treatment (4h or 8h at 5°C per day). All ten isolates survived 3days of cycled heat treatment and resumed normal growth afterward; some isolates however, were considerably more negatively affected by heat-cycling than others. In fact, some isolates underwent greatly reduced growth not only during 8h heating, but also some hours after cessation of heat treatment. This phenomenon is labeled in the current study as "post-stress growth delay" (PSGD). In contrast, all isolates stopped growing during 8h cold treatments, but immediately recommenced growing on return to 28°C. The delay in recommencing growth of some isolates after heat treatment amplifies the effect of this stress. In addition to the studies on the effects of heat cycling on fungal cultures, the effects of imposing such temperature cycling on fungal infection of insects was documented in the laboratory. Three Metarhizium isolates were bioassayed using Galleria mellonella larvae. Treated insects were placed at daily temperature regimes matching those used for the in vitro fungus rate-of-growth study, and insect mortality recorded daily. For all three isolates the levels of insect mortality at the highest-heat dose (40°C at 8h daily) significantly reduced infection. Fluctuating temperatures are likely to be a factor in most pest-insect habitats; therefore, the presence and level of PSGD of each isolate should be a primary consideration in selecting field-appropriate fungal isolates.

Asphyxiation of Metarhizium robertsii during mycelial growth produces conidia with increased stress tolerance via increased expression of stress-related genes.

Little is known about the impact of hypoxia and anoxia during mycelial growth on tolerance to different stress conditions of developing fungal conidia. Conidia of the insect-pathogenic fungus Metarhizium robertsii were produced on potato dextrose agar (PDA) medium under normoxia (control = normal oxygen concentrations), continuous hypoxia, and transient anoxia, as well as minimal medium under normoxia. The tolerance of the conidia produced under these different conditions was evaluated in relation to wet heat (heat stress), menadione (oxidative stress), potassium chloride (osmotic stress), UV radiation, and 4-nitroquinoline-1-oxide (=4-NQO genotoxic stress). Growth under hypoxic condition induced higher conidial tolerance of M. robertsii to menadione, KCl, and UV radiation. Transient anoxic condition induced higher conidial tolerance to KCl and UV radiation. Nutritional stress (i.e., minimal medium) induced higher conidial tolerance to heat, menadione, KCl, and UV radiation. However, neither of these treatments induced higher tolerance to 4-NQO. The gene hsp30 and hsp101 encoding a heat shock protein was upregulated under anoxic condition. In conclusion, growth under hypoxia and anoxia produced conidia with higher stress tolerances than conidia produced in normoxic condition. The nutritive stress generated by minimal medium, however, induced much higher stress tolerances. This condition also caused the highest level of gene expression in the hsp30 and hsp101 genes. Thus, the conidia produced under nutritive stress, hypoxia, and anoxia had greater adaptation to stress.

Conidial mass production of entomopathogenic fungi and tolerance of their mass-produced conidia to UV-B radiation and heat.

We investigated conidial mass production of eight isolates of six entomopathogenic fungi (EPF), Aphanocladium album (ARSEF 1329), Beauveria bassiana (ARSEF 252 and 3462), Lecanicillium aphanocladii (ARSEF 6433), Metarhizium anisopliae sensu lato (ARSEF 2341), Metarhizium pingshaense (ARSEF 1545), and Simplicillium lanosoniveum (ARSEF 6430 and 6651) on white or brown rice at four moisture conditions (75-100%). The tolerance of mass-produced conidia of the eight fungal isolates to UV-B radiation and heat (45 °C) were also evaluated. For each moisture content compared, a 20-g sample of rice in a polypropylene bag was inoculated with each fungal isolate in three replicates and incubated at 28 ± 1 °C for 14 days. Conidia were then harvested by washing the substrate, and conidial concentrations determined by haemocytometer counts. Conidial suspensions were inoculated on PDAY with 0.002% benomyl in Petri plates and exposed to 978 mW m-2 of Quaite-weighted UV-B for 2 h. Additionally, conidial suspensions were exposed to 45 °C for 3 h, and aliquots inoculated on PDAY with benomyl. The plates were incubated at 28 ± 1 °C, and germination was assessed at 400 × magnification after 48 h. Conidial production was generally higher on white rice than on brown rice for all fungal species, except for L. aphanocladii ARSEF 6433, regardless of moisture combinations. The 100% moisture condition provided higher conidial production for B. bassiana (ARSEF 252 and ARSEF 3462) and M. anisopliae (ARSEF 2341) isolates, while the addition of 10% peanut oil enhanced conidial yield for S. lanosoniveum isolate ARSEF 6430. B. bassiana ARSEF 3462 on white rice with 100% water yielded the highest conidial production (approximately 1.3 × 1010 conidia g-1 of substrate). Conidia produced on white rice with the different moisture conditions did not differ in tolerance to UV-B radiation or heat. However, high tolerance to UV-B radiation and heat was observed for B. bassiana, M. anisopliae, and A. album isolates. Heat-treated conidia of S. lanosoniveum and L. aphanocladii did not germinate.

Dosimetric measurements of Onyx embolization material for stereotactic radiosurgery.

PURPOSE: Arteriovenous malformations are often treated with a combination of embolization and stereotactic radiosurgery. Concern has been expressed in the past regarding the dosimetric properties of materials used in embolization and the effects that the introduction of these materials into the brain may have on the quality of the radiosurgery plan. To quantify these effects, the authors have taken large volumes of Onyx 34 and Onyx 18 (ethylene-vinyl alcohol copolymer doped with tantalum) and measured the attenuation and interface effects of these embolization materials. METHODS: The manufacturer provided large cured volumes (∼28 cc) of both Onyx materials. These samples were 8.5 cm in diameter with a nominal thickness of 5 mm. The samples were placed on a block tray above a stack of solid water with an Attix chamber at a depth of 5 cm within the stack. The Attix chamber was used to measure the attenuation. These measurements were made for both 6 and 16 MV beams. Placing the sample directly on the solid water stack and varying the thickness of solid water between the sample and the Attix chamber measured the interface effects. The computed tomography (CT) numbers for bulk material were measured in a phantom using a wide bore CT scanner. RESULTS: The transmission through the Onyx materials relative to solid water was approximately 98% and 97% for 16 and 6 MV beams, respectively. The interface effect shows an enhancement of approximately 2% and 1% downstream for 16 and 6 MV beams. CT numbers of approximately 2600-3000 were measured for both materials, which corresponded to an apparent relative electron density (RED) ρ(e) (w) to water of approximately 2.7-2.9 if calculated from the commissioning data of the CT scanner. CONCLUSIONS: We performed direct measurements of attenuation and interface effects of Onyx 34 and Onyx 18 embolization materials with large samples. The introduction of embolization materials affects the dose distribution of a MV therapeutic beam, but should be of negligible consequence for effective thicknesses of less than 8 mm. The measured interface effects are also small, particularly at 6 MV. Large areas of high-density artifacts and low-density artifacts can cause errors in dose calculations and need to be identified and resolved during planning.

Penalization of aperture complexity in inversely planned volumetric modulated arc therapy.

PURPOSE: Apertures obtained during volumetric modulated arc therapy (VMAT) planning can be small and irregular, resulting in dosimetric inaccuracies during delivery. Our purpose is to develop and integrate an aperture-regularization objective function into the optimization process for VMAT, and to quantify the impact of using this objective function on dose delivery accuracy and optimized dose distributions. METHODS: An aperture-based metric ("edge penalty") was developed that penalizes complex aperture shapes based on the ratio of MLC side edge length and aperture area. To assess the utility of the metric, VMAT plans were created for example paraspinal, brain, and liver SBRT cases with and without incorporating the edge penalty in the cost function. To investigate the dose calculation accuracy, Gafchromic EBT2 film was used to measure the 15 highest weighted apertures individually and as a composite from each of two paraspinal plans: one with and one without the edge penalty applied. Films were analyzed using a triple-channel nonuniformity correction and measurements were compared directly to calculations. RESULTS: Apertures generated with the edge penalty were larger, more regularly shaped and required up to 30% fewer monitor units than those created without the edge penalty. Dose volume histogram analysis showed that the changes in doses to targets, organs at risk, and normal tissues were negligible. Edge penalty apertures that were measured with film for the paraspinal plan showed a notable decrease in the number of pixels disagreeing with calculation by more than 10%. For a 5% dose passing criterion, the number of pixels passing in the composite dose distributions for the non-edge penalty and edge penalty plans were 52% and 96%, respectively. Employing gamma with 3% dose/1 mm distance criteria resulted in a 79.5% (without penalty)/95.4% (with penalty) pass rate for the two plans. Gradient compensation of 3%/1 mm resulted in 83.3%/96.2% pass rates. CONCLUSIONS: The use of the edge penalty during optimization has the potential to markedly improve dose delivery accuracy for VMAT plans while still maintaining high quality optimized dose distributions. The penalty regularizes aperture shape and improves delivery efficiency.

Perspectives on the potential of entomopathogenic fungi in biological control of ticks.

Ticks are serious health threats for humans, and both domestic and wild animals. Ticks are controlled mostly by application of chemical products; but these acaricides have several negative side effects, including toxicity to animals, environmental contamination, and induction of chemical resistance in some tick populations. Entomopathogenic fungi infect arthropods in nature and can occur at enzootic or epizootic levels in their host populations. Laboratory studies clearly demonstrate that these fungi can cause high mortality in all developmental stages of several tick species, and also reduce oviposition of infected engorged females. Tick mortality following application of fungi in the field, however, often is less than that suggested by laboratory tests. This is due to many negative biotic and climatic factors. To increase efficacy of fungal agents for biological control of ticks under natural conditions, several points need consideration: (1) select effective isolates (viz., high virulence; and tolerance to high temperature, ultraviolet radiation and desiccation); (2) understand the main factors that affect virulence of fungal isolates to their target arthropods including the role of toxic metabolites of the fungal isolates; and (3) define with more precision the immune response of ticks to infection by entomopathogenic fungi. The current study reviews recent literature on biological control of ticks, and comments on the relevance of these results to advancing the development of fungal biocontrol agents, including improving formulation of fungal spores for use in tick control, and using entomopathogenic fungi in integrated pest (tick) management programs.