Frequencies and distribution of kdr and Ace alleles that cause insecticide resistance in house flies in the United States.

House flies (Musca domestica L) are nuisances and vectors of pathogens between and among humans and livestock. Population suppression has been accomplished for decades with pyrethroids and acetylcholinesterase (AChE) inhibitors, but recurrent selection has led to increased frequency of alleles conferring resistance to those two classes of active ingredients (Geden et al., 2021). A common mechanism of resistance to both classes involves an altered target site (mutations in Voltage gated sodium channel (Vgsc) for pyrethroids or in Ace for AChE inhibitors). As part of ongoing efforts to understand the origin, spread and evolution of insecticide resistance alleles in house fly populations, we sampled flies in 11 different US states, sequenced, and then estimated frequencies of the Vgsc and Ace alleles. There was substantial variation in frequencies of the four common knockdown resistance alleles (kdr (L1014F), kdr-his (L1014H), super-kdr (M918T + L10414F) and 1B (T929I + L1014F) across the sampled states. The kdr allele was found in all 11 states and was the most common allele in four of them. The super-kdr allele was detected in only six collections, with the highest frequencies found in the north, northeast and central United States. The kdr-his allele was the most common allele in PA, NC, TN and TX. In addition, a novel super-kdr-like mutation in mutually exclusive exon 17a was found. The overall frequencies of the different Ace alleles, which we name based on the amino acid present at the mutation sites (V260L, A316S, G342A/V and F407Y), varied considerably between states. Five Ace alleles were identified: VAGF, VAVY, VAGY, VAAY and VSAY. Generally, the VSAY allele was the most common in the populations sampled. The susceptible allele (VAGF) was found in all populations, ranging in frequency from 3% (KS) to 41% (GA). Comparisons of these resistance allele frequencies with those previously found suggests a dynamic interaction between the different alleles, in terms of levels of resistance they confer and likely fitness costs they impose in the absence of insecticides.

Frequency of errors in the transfer of treatment parameters from the treatment planning system to the oncology information system in a multi-vendor environment.

BACKGROUND: Technological advancements have made it possible to improve patient outcomes in radiotherapy, sparing both normal tissues and increasing tumour control. However, these advancements have resulted in an increase in the number of software systems used, which each require data inputs to function. For institutions with multiple vendors for their treatment planning systems and oncology information systems, the transfer of data between them is potentially error prone and can lead to treatment errors. PURPOSE: The goal of this work was to determine the frequency of errors in data transfers between the Varian Eclipse treatment planning system and the Elekta Mosaiq oncology information system. METHODS: An in-house program was used to quantify the number of errors for 2700 unique plans over an 8-month period. Using this information, the frequency of the errors were calculated. A risk priority number was calculated using the calculated frequencies to determine the impact on the clinic. RESULTS: The most common errors discovered were backup timer settings (10.7%), Field label (8.5%), DRR associations (3.3%), imaging field types (3.1%), dose rate (1%), Field Id (0.8%), imaging isocenter (0.7% and SSD (0.7%). Based on the risk priority numbers, the DRR association error was ranked as having the highest potential impact on the patient. CONCLUSIONS: The results of the work show that the most effort should be focused on checking the manual steps performed in the transfer process, while items that are imported directly from DICOM-RT without modification are highly likely to be transferred accurately. The data can be used to help guide the implementation of future automated tools and process improvement in the clinic.

Emergency Department Management of the Covid-19 Pandemic.

BACKGROUND: Emergency departments (EDs) need to be prepared to manage crises and disasters in both the short term and the long term. The coronavirus disease 2019 (COVID-19) pandemic has necessitated a rapid overhaul of several aspects of ED operations in preparation for a sustained response. OBJECTIVE: We present the management of the COVID-19 crisis in 3 EDs (1 large academic site and 2 community sites) within the same health care system. DISCUSSION: Aspects of ED throughput, including patient screening, patient room placement, and disposition are reviewed, along with departmental communication procedures and staffing models. Visitor policies are also discussed. Special considerations are given to airway management and the care of psychiatric patients. Brief guidance around the use of personal protective equipment is also included. CONCLUSIONS: A crisis like the COVID-19 pandemic requires careful planning to facilitate urgent restructuring of many aspects of an ED. By sharing our departments' responses to the COVID-19 pandemic, we hope other departments can better prepare for this crisis and the next.

Mapping and sequencing of structural variation from eight human genomes.

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

Wie wir es heute mit der Religion halten. Liebe und Liebesgeschichten als Antwort auf die Gretchenfrage ­ eine Untersuchung zu Goethe und Honigmann.

Like the shaded area belonging equally to two overlapping circles in a Venn diagram, love may be experienced as both essentially religious and as a moment of secular transcendence. Faust exploits this convergence in his famous response to Gretchen. Honigmann both reverses and expands upon this "Faustian accommodation," revealing how love within a modern, secular society might stand in for - and also with - traditional religious affiliation.

Stray neutron radiation exposures from proton therapy: physics-based analytical models of neutron spectral fluence, kerma and absorbed dose.

Objective. Patients who receive proton beam therapy are exposed to unwanted stray neutrons. Stray radiations increase the risk of late effects in normal tissues, such as second cancers and cataracts, and may cause implanted devices such as pacemakers to malfunction. Compared to therapeutic beams, little attention has been paid to modeling stray neutron exposures. In the past decade, substantial progress was made to develop semiempirical models of stray neutron dose equivalent, but models to routinely calculate neutron absorbed dose and kerma are still lacking. The objective of this work was to develop a new physics based analytical model to calculate neutron spectral fluence, kerma, and absorbed dose in a water phantom.Approach. We developed the model using dosimetric data from Monte Carlo simulations and neutron kerma coefficients from the literature. The model explicitly considers the production, divergence, scattering, and attenuation of neutrons. Neutron production was modeled for 120-250 MeV proton beams impinging on a variety of materials. Fluence, kerma and dose calculations were performed in a 30 × 180 × 44 cm3phantom at points up to 43 cm in depth and 80 cm laterally.Main Results. Predictions of the analytical model agreed reasonably with corresponding values from Monte Carlo simulations, with a mean difference in average energy deposited of 20%, average kerma coefficient of 21%, and absorbed dose to water of 49%.Significance. The analytical model is simple to implement and use, requires less configuration data that previously reported models, and is computationally fast. This model appears potentially suitable for integration in treatment planning system, which would enable risk calculations in prospective and retrospective cases, providing a powerful tool for epidemiological studies and clinical trials.

Personalized 3D-printed anthropomorphic phantoms for dosimetry in charged particle fields.

Anthropomorphic phantoms used for radiation dose measurements are designed to mimic human tissue in shape, size, and tissue composition. Reference phantoms are widely available and are sufficiently similar to many, but not all, human subjects. 3D printing has the potential to overcome some of these shortcomings by enabling rapid fabrication of personalized phantoms for individual human subjects based on radiographic imaging data.Objective. The objective of this study was to test the efficacy of personalized 3D printed phantoms for charged particle therapy. To accomplish this, we measured dose distributions from 6 to 20 MeV electron beams, incident on printed and molded slices of phantoms.Approach. Specifically, we determined the radiological properties of 3D printed phantoms, including beam penetration range. Additionally, we designed and printed a personalized head phantom to compare results obtained with a commercial, reference head phantom for quality assurance of therapeutic electron beam dose calculations.Main Results. For regions of soft tissue, gamma index analyses revealed a 3D printed slice was able to adequately model the same electron beam penetration ranges as the molded reference slice. The printed, personalized phantom provided superior dosimetric accuracy compared to the molded reference phantom for electron beam dose calculations at all electron beam energies. However, current limitations in the ability to print high-density structures, such as bone, limited pass rates of 60% or better at 16 and 20 MeV electron beam energies.Significance. This study showed that creating personalized phantoms using 3D printing techniques is a feasible way to substantially improve the accuracy of dose measurements of therapeutic electron beams, but further improvements in printing techniques are necessary in order to increase the printable density in phantoms.

Light whole genome sequence for SNP discovery across domestic cat breeds.

BACKGROUND: The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus--FeLV, feline coronavirus--FECV, feline immunodeficiency virus--FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery. DESCRIPTION: To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower-limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%. CONCLUSIONS: These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases.

Computational feasibility of simulating whole-organ vascular networks.

The human body contains approximately 20 billion blood vessels, which transport nutrients, oxygen, immune cells, and signals throughout the body. The brain's vasculature includes up to 9 billion of these vessels to support cognition, motor processes, and myriad other vital functions. To model blood flowing through a vasculature, a geometric description of the vessels is required. Previously reported attempts to model vascular geometries have produced highly-detailed models. These models, however, are limited to a small fraction of the human brain, and little was known about the feasibility of computationally modeling whole-organ-sized networks. We implemented a fractal-based algorithm to construct a vasculature the size of the human brain and evaluated the algorithm's speed and memory requirements. Using high-performance computing systems, the algorithm constructed a vasculature comprising 17 billion vessels in 1960 core-hours, or 49 minutes of wall-clock time, and required less than 32 GB of memory per node. We demonstrated strong scalability that was limited mainly by input/output operations. The results of this study demonstrated, for the first time, that it is feasible to computationally model the vasculature of the whole human brain. These findings provide key insights into the computational aspects of modeling whole-organ vasculature.

Computational feasibility of simulating changes in blood flow through whole-organ vascular networks from radiation injury.

Vasculature is necessary to the healthy function of most tissues. In radiation therapy, injury of the vasculature can have both beneficial and detrimental effects, such as tumor starvation, cardiac fibrosis, and white-matter necrosis. These effects are caused by changes in blood flow due to the vascular injury. Previously, research has focused on simulating the radiation injury of vasculature in small volumes of tissue, ignoring the systemic effects of local damage on blood flow. Little is known about the computational feasibility of simulating the radiation injury to whole-organ vascular networks. The goal of this study was to test the computational feasibility of simulating the dose deposition to a whole-organ vascular network and the resulting change in blood flow. To do this, we developed an amorphous track-structure model to transport radiation and combined this with existing methods to model the vasculature and blood flow rates. We assessed the algorithm's computational scalability, execution time, and memory usage. The data demonstrated it is computationally feasible to calculate the radiation dose and resulting changes in blood flow from 2 million protons to a network comprising 8.5 billion blood vessels (approximately the number in the human brain) in 87 hours using a 128-node cluster. Furthermore, the algorithm demonstrated both strong and weak scalability, meaning that additional computational resources can reduce the execution time further. These results demonstrate, for the first time, that it is computationally feasible to calculate radiation dose deposition in whole-organ vascular networks. These findings provide key insights into the computational aspects of modeling whole-organ radiation damage. Modeling the effects radiation has on vasculature could prove useful in the study of radiation effects on tissues, organs, and organisms.

Computational feasibility of calculating the steady-state blood flow rate through the vasculature of the entire human body.

The human body contains approximately 20 billion individual blood vessels that deliver nutrients and oxygen to tissues. While blood flow is a well-developed field of research, no previous studies have calculated the blood flow rates through more than 5 million connected vessels. The goal of this study was to test if it is computationally feasible to calculate the blood flow rates through a vasculature equal in size to that of the human body. We designed and implemented a two-step algorithm to calculate the blood flow rates using principles of steady-state fluid dynamics. Steady-state fluid dynamics is an accurate approximation for the microvascular and venous structures in the human body. To determine the computational feasibility, we measured and evaluated the execution time, scalability, and memory usage to quantify the computational requirements. We demonstrated that it is computationally feasible to calculate the blood flow rate through 17 billion vessels in 6.5 hours using 256 compute nodes. The computational modeling of blood flow rate in entire organisms may find application in research on drug delivery, treatment of cancer metastases, and modulation of physiological performance.

Efficacy of Novaluron + Pyriproxyfen (Tekko Pro) Insect Growth Regulators Against Amblyomma americanum (Acari: Ixodidae), Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) microplus, and Rhipicephalus sanguineus.

Ixodids are globally distributed pests that transmit many disease agents. Increasing resistance to conventional acaricides raises the need for alternative tactics. Novaluron and pyriproxyfen are insect growth regulators (IGRs) that have variable potencies against acarines. We conducted in vitro and in vivo experiments to assess novaluron + pyriproxyfen (marketed as Tekko Pro) against four ixodid species. Laboratory assays on the brown dog tick, Rhipicephalus sanguineus (Latreille) (Ixodida: Ixodidae), and the lone star tick, Amblyomma americanum (L.) (Ixodida: Ixodidae), reduced metabolic activity in larvae and nymphs. Concentrations of novaluron + pyriproxyfen dried on filter paper impeded molting of larval R. sanguineus (less effective against nymphs). Molting A. americanum larvae were reduced by >95% using 4 and 8 µg/cm2 eliminated molting; nymphal molting was reduced but not halted even at 16 µg/cm2. On calves, novaluron + pyriproxyfen stopped larval A. americanum metabolic function 1 d post-treatment and larvae did not molt. When larvae were released 30 d after treatment, metabolic activity was reduced by 95% and molting was reduced by 94%. Southern cattle fever tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Ixodida: Ixodidae), larvae released 1 d after treatment on calves were 99% prevented from reaching adulthood. The treatment did not interfere with larval development when larvae were released 52 d after treatment. The cattle fever tick, Rhipicephalus (Boophilus) annulatus (Say) (Ixodida: Ixodidae), failed to reach adulthood when larvae were released on calves a day after treatment (residual activity was not assessed for R. annulatus). These IGRs, and possibly others, offer an alternative to conventional acaricides for ixodid control on cattle.

Lethal Effects of the Insect Growth Regulator Cyromazine Against Three Species of Filth Flies, Musca domestica, Stomoxys calcitrans, and Fannia canicularis (Diptera: Muscidae) in Cattle, Swine, and Chicken Manure.

The presence of various species of filth flies is a widespread problem where livestock, including poultry, are maintained and where manure accumulates. The house fly, Musca domestica L.; the stable fly, Stomoxys calcitrans (L.); and the little house fly, Fannia canicularis (L.) (each Diptera: Muscidae), the target pests in our study, can mechanically spread diseases, and S. calcitrans can bite cattle, causing losses in meat and milk production. Chemical control is widely used to suppress filth flies, but resistance to conventional insecticides has become problematic. Hence, an alternative approach, insect growth regulators (IGRs), has been adopted by many livestock producers. We assessed the ability of the IGR cyromazine in granular and granular-based aqueous formulations to suppress the three muscid species from developing in poultry, cattle, and swine manure collected from commercial livestock production facilities. Each of the two formulations provided either strong or complete control of the pests for the 4-wk duration of the study, excluding the granular formulation that provides control of only F. canicularis developing in poultry manure for 2 wk. The two cyromazine-based IGR formulations appear to be effective tools that, if rotated appropriately with other insecticides, can be incorporated into integrated pest management strategies for filth fly suppression.

Rapid gene cloning using terminator primers and modular vectors.

We seek to create useful biological diversity by exploiting the modular nature of genetic information. In this report we describe experiments that focus on the modular nature of plasmid cloning vectors. Bacterial plasmids are modular entities composed of origins of replication, selectable markers and other components. We describe a new ligation-independent cloning method that allows for rapid and seamless assembly of vectors from component modules. We further demonstrate that gene cloning can be accomplished simultaneously with assembly of a modular vector. This approach provides considerable flexibility as it allows for 'menu driven' cloning of genes into custom assembled modular vectors.

Analytical model for ion stopping power and range in the therapeutic energy interval for beams of hydrogen and heavier ions.

Many different approaches exist to calculate stopping power and range of protons and heavy charged particles. These methods may be broadly categorized as physically complete theories (widely applicable and complex) or semi-empirical approaches (narrowly applicable and simple). However, little attention has been paid in the literature to approaches that are both widely applicable and simple. We developed simple analytical models of stopping power and range for ions of hydrogen, carbon, iron, and uranium that spanned intervals of ion energy from 351 keV u(-1) to 450 MeV u(-1) or wider. The analytical models typically reproduced the best-available evaluated stopping powers within 1% and ranges within 0.1 mm. The computational speed of the analytical stopping power model was 28% faster than a full-theoretical approach. The calculation of range using the analytic range model was 945 times faster than a widely-used numerical integration technique. The results of this study revealed that the new, simple analytical models are accurate, fast, and broadly applicable. The new models require just 6 parameters to calculate stopping power and range for a given ion and absorber. The proposed model may be useful as an alternative to traditional approaches, especially in applications that demand fast computation speed, small memory footprint, and simplicity.

Initial environmental impacts of the Obed Mountain coal mine process water spill into the Athabasca River (Alberta, Canada).

On October 31, 2013, a catastrophic release of approximately 670,000m(3) of coal process water occurred as the result of the failure of the wall of a post-processing settling pond at the Obed Mountain Mine near Hinton, Alberta. A highly turbid plume entered the Athabasca River approximately 20km from the mine, markedly altering the chemical composition of the Athabasca River as it flowed downstream. The released plume traveled approximately 1100km downstream to the Peace-Athabasca Delta in approximately four weeks, and was tracked both visually and using real-time measures of river water turbidity within the Athabasca River. The plume initially contained high concentrations of nutrients (nitrogen and phosphorus), metals, and polycyclic aromatic hydrocarbons (PAHs); some Canadian Council of Ministers of the Environmental (CCME) Guidelines were exceeded in the initial days after the spill. Subsequent characterization of the source material revealed elevated concentrations of both metals (arsenic, lead, mercury, selenium, and zinc) and PAHs (acenaphthene, fluorene, naphthalene, phenanthrene, and pyrene). While toxicity testing using the released material indicated a relatively low or short-lived acute risk to the aquatic environment, some of the water quality and sediment quality variables are known carcinogens and have the potential to exert negative long-term impacts.

Spatiotemporal patterns of mercury accumulation in lake sediments of western North America.

For the Western North America Mercury Synthesis, we compiled mercury records from 165 dated sediment cores from 138 natural lakes across western North America. Lake sediments are accepted as faithful recorders of historical mercury accumulation rates, and regional and sub-regional temporal and spatial trends were analyzed with descriptive and inferential statistics. Mercury accumulation rates in sediments have increased, on average, four times (4×) from 1850 to 2000 and continue to increase by approximately 0.2µg/m(2) per year. Lakes with the greatest increases were influenced by the Flin Flon smelter, followed by lakes directly affected by mining and wastewater discharges. Of lakes not directly affected by point sources, there is a clear separation in mercury accumulation rates between lakes with no/little watershed development and lakes with extensive watershed development for agricultural and/or residential purposes. Lakes in the latter group exhibited a sharp increase in mercury accumulation rates with human settlement, stabilizing after 1950 at five times (5×) 1850 rates. Mercury accumulation rates in lakes with no/little watershed development were controlled primarily by relative watershed size prior to 1850, and since have exhibited modest increases (in absolute terms and compared to that described above) associated with (regional and global) industrialization. A sub-regional analysis highlighted that in the ecoregion Northwestern Forest Mountains, <1% of mercury deposited to watersheds is delivered to lakes. Research is warranted to understand whether mountainous watersheds act as permanent sinks for mercury or if export of "legacy" mercury (deposited in years past) will delay recovery when/if emissions reductions are achieved.