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Introduction: With rising cases of renal cell carcinoma (RCC), precise identification of tumor subtypes is essential, particularly for detecting small, heterogenous lesions often overlooked in traditional histopathological examinations. This study demonstrates the non-invasive use of deep learning for Histopathological differentiation of renal tumors through quadriphasic multidetector computed tomography (MDCT)., Patients and Methods: This prospective longitudinal study includes 50 subjects (32 males, 18 females) with suspected renal tumors. A deep neural network (DNN) is developed to predict RCC subtypes using peak attenuation values measured in Hounsfield Units (HUs) obtained from quadriphasic MDCT scans. The network then generates confidence scores for each of the four primary subtypes of renal tumors, effectively distinguishing between benign oncocytoma and various malignant subtypes., Results: Our neural network accurately distinguishes Renal tumor subtypes, including clear cell, papillary, chromophobe, and benign oncocytoma, with a confidence score of 68% with the network's diagnosis aligning with Histopathological examinations. Our network was also able to accurately classify RCC subtypes on a synthetically generated dataset with 20,000 samples., Conclusion: We developed an artificial intelligence-based RCC subtype classification technique. Our approach is non-invasive and has the potential to transform the methodology in Renal oncology by providing accurate and timely diagnostic information and enhancing clinical decisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Myers et al.)

Mutant B.4.1 , generated via EMS mutagenesis in Drosophila melanogaster , was studied by undergraduate students participating in the Fly-CURE. After inducing genetically mosaic tissue in the adult eye, B.4.1 mutant tissue displays a robust increase in cell division and a rough appearance. Complementation mapping and sequence analysis identified a nonsense mutation in the gene CG1603 , which we named clifford ( cliff ) due to observed increases in red-pigmented mutant tissue compared to controls. cliff encodes a zinc finger-containing protein implicated in transcriptional control. RNAi knockdown of cliff similarly results in rough eyes, confirming a role for Cliff in eye development., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Objective: Intravenous microbubble oscillation in the presence of ultrasound has the potential to yield a wide range of therapeutic benefits. However, the likelihood of vessel damage caused by mechanical effects has not been quantified as a function of the numerous important parameters in therapeutic ultrasound procedures. In this study, we examined the effects of microbubbles injected into the vasculature of the earthworm. It was found that the elastic properties of earthworm blood vessels are similar to those of arteries in older humans, and that earthworms are well suited to the large number of experiments necessary to investigate safety of procedures involving microbubble oscillation in sonicated vessels., Methods: Microbubbles were infused into earthworm vessels, and the rupture time during sonication was recorded as a function of ultrasound frequency, pulse repetition frequency and acoustic pressure., Discussion: A modified mechanical index (MMI) was defined that successfully captured the trends in rupture probability and rupture time for the different parameter values, creating a database of vessel rupture thresholds. In the absence of bubbles, the product of MMI squared and rupture time was approximately constant, indicating a possible radiation-force effect., Conclusion: The MMI was an effective correlating parameter in the presence of bubbles, though the mathematical dependence is not yet apparent. The results of the study are expected to be valuable in designing more refined studies in vertebrate models, as well as informing computational models., Competing Interests: Conflict of interest The authors declare no competing interests., (Published by Elsevier Inc.)

Many facultative and obligate anaerobes reduce perchlorate. Likewise, carbon monoxide (CO) oxidation has been documented in many aerobes, facultative anaerobes, and obligate anaerobes. A molybdenum-dependent CO dehydrogenase (Mo-CODH) and a nickel-dependent CO dehydrogenase (Ni-CODH) distinguish the former from the latter. Some Mo-dependent CO oxidizers (Mo-COX) couple CO oxidation to perchlorate reduction, but only at low concentrations of both under conditions that do not support growth in cultures. In contrast, CO-coupled perchlorate reduction has not been documented in Ni-dependent CO oxidizers (Ni-COX). To assess the potential for Ni-COX to reduce perchlorate, a model, obligately anaerobic homoacetogen, Moorella glycerini DSM 11254 T , was cultivated with or without perchlorate, usiing CO or glycerol as its sole carbon and energy source. It grew with glycerol with or without perchlorate, and its maximum cell densities were only weakly affected by the perchlorate. However, when CO (at a 30% headspace concentration) was used as a carbon and energy source, perchlorate reduction supported greater cell densities and more rapid growth rates. The stoichiometry of CO uptake, perchlorate reduction, and chloride production were consistent with the cryptic pathway for perchlorate reduction with chlorite as an end product. Chloride production occurred abiologically in the medium due to a reaction between chlorite and the sulfide used as a reducing agent. These results provide the first demonstration of CO-coupled perchlorate reduction supporting growth in Ni-COX, and they provide constraints on the potential for perchlorate-coupled, anaerobic CO oxidation in engineered systems as well as terrestrial systems and hypothetical, sub-surface, serpentinite-hosted systems on Mars.

Misconnections between enteral devices and other medical devices have been associated with patient death and serious injuries. To minimize such misconnections, the design of connectors on enteral devices has been standardized. The most common adaptation of the standardized enteral connector is called ENFit. Gastrostomy tubes (G-tubes), which may or may not possess the ENFit connector, are increasingly used to deliver commercial and blenderized diets in home settings to enteral device users. To investigate and compare the performance of G-tubes with and without ENFit connectors, research investigations have recently been performed. However, synthesis of such investigations and quantitative discussion of the consequences of transitioning to ENFit-based G-tube devices has not yet occurred. Here we review the research findings from these studies, with data on patient practices from a Mayo Clinic survey, to estimate the impact on tube feeders in home settings of transitioning to ENFit-based G-tube devices. Extrapolating the findings from these studies to US enteral G-tube patients, 1.5%-8.6% of adult patients and 0.2%-1.9% of pediatric patients may experience perceptible slowing in their gravity feeds if using ENFit-based G-tube devices. About 2.5%-8.6% of adult patients and 0.5%-5.5% of pediatric patients (or their caregivers) may need to push with perceptibly more force for syringe push-based feeding using ENFit-based G-tube devices. Lastly, the article offers suggestions for patients and device manufacturers. [Correction added on 2 May 2022, after first online publication: In the preceding sentence, the percentage of adult patients was revised from 2.5%-8.6% to 1.5%-8.6%.]., (© 2022 American Society for Parenteral and Enteral Nutrition.)

As the climate evolves over the next century, the interaction of accelerating sea level rise (SLR) and storms, combined with confining development and infrastructure, will place greater stresses on physical, ecological, and human systems along the ocean-land margin. Many of these valued coastal systems could reach "tipping points," at which hazard exposure substantially increases and threatens the present-day form, function, and viability of communities, infrastructure, and ecosystems. Determining the timing and nature of these tipping points is essential for effective climate adaptation planning. Here we present a multidisciplinary case study from Santa Barbara, California (USA), to identify potential climate change-related tipping points for various coastal systems. This study integrates numerical and statistical models of the climate, ocean water levels, beach and cliff evolution, and two soft sediment ecosystems, sandy beaches and tidal wetlands. We find that tipping points for beaches and wetlands could be reached with just 0.25 m or less of SLR (~ 2050), with > 50% subsequent habitat loss that would degrade overall biodiversity and ecosystem function. In contrast, the largest projected changes in socioeconomic exposure to flooding for five communities in this region are not anticipated until SLR exceeds 0.75 m for daily flooding and 1.5 m for storm-driven flooding (~ 2100 or later). These changes are less acute relative to community totals and do not qualify as tipping points given the adaptive capacity of communities. Nonetheless, the natural and human built systems are interconnected such that the loss of natural system function could negatively impact the quality of life of residents and disrupt the local economy, resulting in indirect socioeconomic impacts long before built infrastructure is directly impacted by flooding., (© 2021. The Author(s).)

In the absence of fit-testing, leakage of aerosolized pathogens through the gaps between the face and N95 respirators could compromise the effectiveness of the device and increase the risk of infection for the exposed population. To address this issue, we have developed a model to estimate the increase in risk of infection resulting from aerosols leaking through gaps between the face and N95 respirators. The gaps between anthropometric face-geometry and N95 respirators were scanned using computed tomography. The gap profiles were subsequently input into CFD models. The amount of aerosol leakage was predicted by the CFD simulations. Leakage levels were validated using experimental data obtained using manikins. The computed amounts of aerosol transmitted to the respiratory system, with and without leaks, were then linked to a risk-assessment model to predict the infection risk for a sample population. An influenza outbreak in which 50% of the population deployed respirators was considered for risk assessment. Our results showed that the leakage predicted by the CFD model matched the experimental data within about 13%. Depending upon the fit between the headform and the respirator, the inward leakage for the aerosols ranged between 30 and 95%. In addition, the non-fit-tested respirator lowered the infection rate from 97% (for no protection) to between 42 and 80%, but not to the same level as the fit-tested respirators (12%). The CFD-based leakage model, combined with the risk-assessment model, can be useful in optimizing protection strategies for a given population exposed to a pathogenic aerosol.

Although vertebrates are indispensable to biomedical research, studies are often limited by factors such as cost, lengthy internal review, and ethical considerations. We present the earthworm as an alternative, low-cost, invertebrate applicable to certain preliminary vasculature studies. Due to the surgical availability of the earthworm's dorsal vessels, ventral vessels, and five pairs of pseudo hearts, earthworms are readily accessible, offer low-cost maintenance, and require administration of only small doses of a given compound. The earthworm model provides a simple closed vascular circulatory system with a hemoglobin structure similar to human blood. A protocol is provided for anaesthetizing the earthworms and performing surgical incisions to expose relevant blood vessels. Micropipettes for compound administration are formed by heating and pulling glass with a pipette puller and using a beveling system to create a micron-scale fine needle tip. The tips are then used with a micropositioner and microinjector to inject arbitrary compounds into the vascular system of an earthworm, repeatably, with the availability of large sample sizes and small compound volumes. Details on the intricacies of injection procedure are provided. The small vessel size of the earthworm is challenging, particularly in the case of the ventral vessel; however, mastery of the techniques presented offers high repeatability as a low-cost solution, making studies of very large sample size practical.

Background: Face coverings constitute an important strategy for containing pandemics, such as COVID-19. Infection from airborne respiratory viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can occur in at least three modes; tiny and/or dried aerosols (typically < 1.0 μm) generated through multiple mechanisms including talking, breathing, singing, large droplets (> 0.5 μm) generated during coughing and sneezing, and macro drops transmitted via fomites. While there is a growing number of studies looking at the performance of household materials against some of these situations, to date, there has not been any systematic characterization of household materials against all three modes., Methods: A three-step methodology was developed and used to characterize the performance of 21 different household materials with various material compositions (e.g. cotton, polyester, polypropylene, cellulose and blends) using submicron sodium chloride aerosols, water droplets, and mucous mimicking macro droplets over an aerosol-droplet size range of ~ 20 nm to 0.6 cm., Results: Except for one thousand-thread-count cotton, most single-layered materials had filtration efficiencies < 20% for sub-micron solid aerosols. However, several of these materials stopped > 80% of larger droplets, even at sneeze-velocities of up to 1700 cm/s. Three or four layers of the same material, or combination materials, would be required to stop macro droplets from permeating out or into the face covering. Such materials can also be boiled for reuse., Conclusion: Four layers of loosely knit or woven fabrics independent of the composition (e.g. cotton, polyester, nylon or blends) are likely to be effective source controls. One layer of tightly woven fabrics combined with multiple layers of loosely knit or woven fabrics in addition to being source controls can have sub-micron filtration efficiencies > 40% and may offer some protection to the wearer. However, the pressure drop across such fabrics can be high (> 100 Pa)., Competing Interests: The authors have declared that no competing interests exist.

Background: Gastrostomy tubes (G-tubes) are typically used when people cannot eat food by mouth. The connector section that allows G-tubes to connect to other devices, such as feeding sets or syringes, has been modified on some of the devices to reduce misconnections in hospital settings. The narrow internal diameter of the new connector, standardized under ISO 80369-3, has caused some users to express concern about a reduced flow rate. Previous studies performed on commercial devices determined that it was not conclusive how much the ISO 80369-3 connector contributed towards the reduced flow rate, because when manufacturers designed these new connector-based devices, they often changed other geometric variables (such as distal tube diameter, or length) at the same time. Thus, it became difficult isolating the effect of the connector from other geometric variables., Method: The key objective of this study was to investigate how different design variables impacted the flow rate through the G-tubes. 3D-printed devices were used to assess the geometric parameters in a systematic manner. Commercial diets and Newtonian analog fluids with matched viscosities were used for testing., Results: The flow path length of the "transition section" encompassing the standardized ISO 80369-3 connector in the new devices was found to cause reduced flow. Additionally, results showed that a shortened (≤ 10 mm) transition section, along with a 10% increase in the distal inner diameter of large bore devices (e.g., 24 Fr), can restore flow rates to levels consistent with the previous devices prior to the connector standardization., Conclusions: The strategy for restoring flow rates to previous levels may help alleviate concerns raised by multiple stakeholders such as health care professionals, patients, caregivers and device manufacturers. In addition, the approach proposed here can be used as a tool for designing future G-tube devices., Competing Interests: The authors have declared that no competing interests exist.

Three novel carbon monoxide-oxidizing Halobacteria were isolated from Bonneville Salt Flats (Utah, USA) salt crusts and nearby saline soils. Phylogenetic analysis of 16S rRNA gene sequences revealed that strains PCN9 T , WSA2 T and WSH3 T belong to the genera Halobacterium , Halobaculum and Halovenus , respectively. Strains PCN9 T , WSA2 T and WSH3 T grew optimally at 40 °C (PCN9 T ) or 50 °C (WSA2 T , WSH3 T ). NaCl optima were 3 M (PCN9 T , WSA2 T ) or 4 M NaCl (WSH3 T ). Carbon monoxide was oxidized by all isolates, each of which contained a molybdenum-dependent CO dehydrogenase. G+C contents for the three respective isolates were 66.75, 67.62, and 63.97 mol% as derived from genome analyses. The closest phylogenetic relatives for PCN9 T , WSA2 T and WSH3 T were Halobacterium noricense A1 T , Halobaculum roseum D90 T and Halovenus aranensis EB27 T with 98.71, 98.19 and 95.95 % 16S rRNA gene sequence similarities, respectively. Genome comparisons of PCN9 T with Halobacterium noricense A1 T yielded an average nucleotide identity (ANI) of 82.0% and a digital DNA-DNA hybridization (dDDH) value of 25.7 %; comparisons of WSA2 T with Halobaculum roseum D90 T yielded ANI and dDDH values of 86.34 and 31.1 %, respectively. The ANI value for a comparison of WSH3 T with Halovenus aranensis EB27 T was 75.2 %. Physiological, biochemical, genetic and genomic characteristics of PCN9 T , WSA2 T and WSH3 T differentiated them from their closest phylogenetic neighbours and indicated that they represent novel species for which the names Halobaculum bonnevillei , Halobaculum saliterrae and Halovenus carboxidivorans are proposed, respectively. The type strains are PCN9 T (=JCM 32472=LMG 31022=ATCC TSD-126), WSA2 T (=JCM 32473=ATCC TSD-127) and WSH3 T (=JCM 32474=ATCC TSD-128).

Study Objective: To determine the ability of tissue containment systems to prevent leakage of cancer cell surrogates when subjected to forces encountered during power morcellation procedures., Design: In vitro study., Setting: Medical device research laboratory., Interventions: Samples from 7 different legally marketed tissue containment bags (1 of which is indicated for power morcellation) were subjected to dye and bacteriophage penetration tests at pressures ranging from 0.5 to 50 times the insufflation pressure. The minimum pressure required to cause bag leakage was measured. Subsequently, the morcellation leakage safety factor for each bag was determined as the ratio of the minimum leakage pressure of the bag to the total pressure contributed from insufflation pressure and mechanical forces acting during the power morcellation procedure., Measurement and Main Results: The leakage performance of the bags varied markedly from brand to brand. No correlation was found between leakage pressure and the bag material or the total bag thickness. The leakage pressures ranged from 26 mmHg to >1293 mmHg for the 7 bags, and safety factors ranged from 1 to 50 when only the insufflation pressure was considered. However, if the morcellation forces were included in the calculation, the safety factor dropped by 6-fold for all brands and dropped below 1, indicating likelihood of leakage, for 2 of the 7 brands., Conclusion: This study provides a mechanism for more realistically simulating the conditions experienced by containment bags during morcellation and quantifying the level of safety provided by the bags., (Published by Elsevier Inc.)

The efficacy of three consecutive monthly treatments with a novel topical product (Revolution ® Plus/Stronghold ® Plus, Zoetis) containing selamectin in combination with the isoxazoline, sarolaner, was compared with that of another topical isoxazoline, fluralaner [Bravecto ® (fluralaner topical solution) for Cats, Merck] against Ixodes scapularis ticks on cats. Twenty-four cats were ranked by pre-treatment tick counts to form groups of three and were randomly allocated to be treated with placebo, the minimum label dosage of Revolution ® Plus (6 mg/kg selamectin plus 1 mg/kg sarolaner) or the minimum label dosage of Bravecto ® for Cats (40 mg/kg fluralaner) within the groups. On Days 0, 30, and 60, each cat in the placebo and Revolution ® Plus-treated groups was treated topically, whereas cats in the Bravecto ® for Cats-treated group were treated topically once on Day 0 with fluralaner and, subsequently, these animals were treated with the placebo on Days 30 and 60 to maintain masking. Doses were calculated based on weight to provide the minimum label dosage for each product; the calculated volume of product to be administered was rounded off to the nearest 0.1 mL. The selamectin plus sarolaner-treated cats received effective dosages of 5.29-7.12 mg/kg selamectin and 0.88-1.19 mg/kg sarolaner, while the fluralaner cats received dosages of 35.21-43.16 mg/kg fluralaner. Cats were infested with approximately 50 unfed viable adult I. scapularis ticks on Days 5, 12, 26, 40, 54, 68, 82, and 88. Efficacy was assessed at 48 h after each infestation. There were no adverse reactions to any treatment during the study. The placebo-treated cats maintained adequate tick infestations throughout the study. Three monthly treatments with selamectin plus sarolaner (Revolution ® Plus) resulted in high and consistent efficacy against I. scapularis for up to 30 days after each treatment. Based on geometric means, efficacy was ≥99.1% at all time points assessed. Treatment with fluralaner (Bravecto ® for Cats) provided high and consistent efficacy of ≥99.3% up to Day 70. On Day 84, efficacy was 90.1%; however, cats from which ticks were recovered on Day 84 had received approximately 4%-12% less than the minimum dosage of 40 mg/kg fluralaner. Three consecutive monthly treatments with Revolution ® Plus or a single treatment with Bravecto ® for Cats provided >90% control of I. scapularis ticks over a 12-week time period., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

Two randomised, single-masked, multi-center field studies were conducted in the United States in cats presented as veterinary patients. The first study evaluated the efficacy and safety of a topically applied formulation of selamectin plus sarolaner (Revolution ® Plus/Stronghold ® Plus, Zoetis) against natural flea infestations; the second study evaluated its efficacy against natural ear mite infestations. The product was administered topically by the cats' owners at the dose range provided in the market product of 6.0-12.0 mg selamectin and 1.0-2.0 mg sarolaner per kg bodyweight. Imidacloprid plus moxidectin (Advantage ® Multi for Cats, Bayer) was used as a positive control in both studies at the label dosage. In the flea study, treatments were administered on Days 0, 30, and 60. Efficacy was calculated based on the mean percent reduction of live flea counts on Days 30, 60, and 90 relative to the pre-treatment count. In the ear mite study, a single treatment was applied on Day 0 and efficacy was determined on Days 14 and 30 based on the presence or absence of ear mites. In both studies, patients were randomly allocated to treatments in the ratio of 2:1, selamectin plus sarolaner: imidacloprid plus moxidectin. In the two studies, 405 cats received treatment with selamectin plus sarolaner; of these, 256 cats received three monthly treatments in the flea study. There were no serious adverse reactions to treatment with selamectin plus sarolaner; health issues noted were typical of the normal ailments or minor traumatic injuries expected in the general cat population and were similar in both treatment groups. Efficacy against fleas based on geometric (arithmetic) means was 97.2% (95.9%), 99.5% (99.4%), and 99.8% (99.8%) in the selamectin plus sarolaner group and was 79.7% (70.5%), 91.4% (77.3%), and 95.5% (87.4%) in the imidacloprid plus moxidectin group on Days 30, 60, and 90, respectively. Flea counts for the selamectin plus sarolaner group were significantly lower than the counts for the imidacloprid plus moxidectin group at all time-points after treatment administration on Day 0 (P <  0.001). Treatment reduced the clinical signs of flea allergy dermatitis (alopecia, dermatitis/pyodermatitis, erythema, pruritus, scaling, and papules) in affected cats by 86.7%-100% in the selamectin plus sarolaner group and by 66.7%-100% in the imidacloprid plus moxidectin group. In the ear mite study, a single application of selamectin plus sarolaner resulted in the clearance of mites from 87.5% of cats within 14 days and 94.4% of cats within 30 days of treatment. The respective percentages of mite-free cats in the imidacloprid plus moxidectin group were 64.0% and 72.0%. There were significantly more cats with no mites noted in the selamectin plus sarolaner group than in the imidacloprid plus moxidectin group on Day 14 and Day 30 (P ≤  0.018). Selamectin plus sarolaner (Revolution ® Plus/Stronghold ® Plus) administered topically at monthly intervals for three months was well tolerated and highly effective for the treatment and prevention of natural infestations of fleas on cats presented as veterinary patients. Clinical signs of flea allergy dermatitis improved in affected cats following treatment administration. A single topical treatment was also safe and highly effective for the treatment of ear mite infestations in naturally infested cats., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

A new topical formulation of selamectin plus sarolaner (Revolution ® Plus/Stronghold ® Plus, Zoetis) was evaluated in the treatment and control of naturally occurring infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States. Three thousand three hundred three (3303) cats were screened in 25 veterinary practices in 15 states and 153 hookworm-positive cats (A. tubaeforme and/or A. braziliense), mainly from Alabama, Mississippi, Texas, and Hawaii, were identified; 135 cats met all the criteria for enrollment and were included on study. The cats were randomly assigned to treatment with Revolution ® (at the label dosage, to provide a minimum dosage of 6 mg/kg selamectin) or selamectin plus sarolaner (at a dosage of 6-12 mg/kg plus 1-2 mg/kg, respectively). Treatments were administered at the time of enrollment and repeated 30 days later. Fecal samples were collected for differential fecal egg count prior to the first treatment (Day 0), prior to the second treatment (Day 30), and approximately 30 days later (Day 60). Efficacy was based on the percentage reductions in geometric mean fecal egg count for A. tubaeforme on Day 30 and Day 60 compared with Day 0. Where cats were co-infected with T. cati, efficacy against this species was also evaluated. Efficacy data were evaluated for A. tubaeforme for 40 cats on both Day 30 and Day 60 for the group treated with the selamectin/sarolaner combination and reductions in geometric mean fecal egg counts of 99.4% and 99.7% were demonstrated for Day 30 and Day 60, respectively. For the group treated with selamectin alone, 44 and 40 cats were evaluated and percent reductions for Day 30 and Day 60 were 99.5% and 99.9%, respectively. For T. cati, 14 cats were evaluated in the selamectin/sarolaner-treated group for Day 30 and for Day 60, and the reduction in geometric mean fecal egg count was 100% for both days. There were 11 and 9 cats evaluated for Day 30 and Day 60, respectively, for the selamectin-treated group and the reduction was again 100% for both days. The geometric mean fecal egg counts post-treatment were significantly lower than pre-treatment for both A. tubaeforme and T. cati, for both treatments, and for both periods of interest (P < 0.0001). No serious adverse events related to treatment with either product occurred during the study. Thus, both selamectin alone and the combination product of selamectin/sarolaner were safe and effective when administered on a monthly basis for the treatment and control of natural infections of A. tubaeforme and T. cati. The addition of sarolaner to the formulation did not interfere with the efficacy of selamectin against these nematodes., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

Objective: Blenderized diets are gaining increasing popularity among enteral tube users. Connectors in gastrostomy tubes (G-tubes) are undergoing standardization to reduce misconnections. These standardized G-tubes are referred to as ENFit G-tubes. This study was performed to quantify the in vitro performance of existing (legacy) G-tubes and compare them with ENFit G-tubes for blenderized diets., Method: Patient blenderized diet recipes and practices were obtained through patient advocacy groups. Different blenders and blending times were studied. Five legacy G-tube brands and three corresponding ENFit brands, sized between 14 Fr and 24 Fr, were studied under gravity and push modes of feeding., Results: Considering both thin and thick blenderized gravity mode diets, an average increase in feeding time from 20 minutes to 32 ± 18 minutes in transitioning from legacy to ENFit was observed with standard G-tubes, compared to 22 ± 3.5 minutes for low profiles. For push-mode diets, a 60-second push with standard ENFit G-tubes was easier compared to standard legacy G-tubes (61% ± 21% as much force), but faster 5-second pushes required considerably more effort for ENFit standard G-tubes (167% ± 96%). Low-profile ENFit G-tubes required slightly less effort compared to low-profile legacies for both 60-second and 5-second pushes (72% ± 22% and 90% ± 19%, respectively). Clogging was common in both legacy and ENFit devices, particularly under gravity mode., Conclusions: For a push mode of feeding, patients will largely be unimpacted after the transition to ENFit. For a gravity mode of feeding, some ENFit users may need higher-powered blenders and should expect increased feeding times.

Adequate cleaning of reusable medical devices is critical for preventing cross-infection among patients. For reusable medical devices, cleaning using mechanical brushes and detergent may not be sufficient to completely remove the infectious contaminants from the surfaces. This study evaluates the role of fluid flow-induced shear stress in the detachment and removal of contaminants from device surfaces. A stainless-steel test coupon, acting as a surrogate for a device surface, was coated with artificial clot of varying mass. The test coupon was exposed to fluid shear stress both with and without an enzymatic detergent. The relationship between clot removal quantity and the applied shear stress was obtained for multiple clot masses. Our results showed that fluid shear increased the effectiveness of the cleaning process. In the absence of flow, soaking the clot surface in the enzymatic detergent removed 67%, 77%, and 95% of the clot for 16 mg, 6.8 mg, and 1 mg initial masses, respectively. In the presence of fluid shear (0.3 Pa for 5 min), approximately 85%, 97%, and 99% of the clot was removed from the surface. The clot mass removed followed a linear relationship (R 2 = 0.98) versus the applied fluid shear stress. This study showed that different cleaning processes such as fluid shear and detergent action contribute to the soil removal process. This method could be used to evaluate cleaning protocols for minimizing contaminant residue after the reprocessing of medical devices. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1132-1140, 2019., (© 2018 Wiley Periodicals, Inc.)

Objectives: For electronic nicotine delivery systems (ENDS), also commonly called e-cigarettes, coil temperature is a factor in the potential production of toxic chemical constituents. However, data are lacking regarding the temperatures that are achieved in the latest generation of these devices. Fourth-generation ENDS are capable of producing heating coil temperatures well above e-liquid boiling points, and allow the user to monitor and set the heating coil temperature during a puff. In this study, we evaluate the accuracy and consistency of the temperature measurement and control settings for different brands of fourth-generation ENDS., Methods: A study was performed using three commercially available, fourth-generation ENDS. The atomizer coil temperatures were obtained from the device (using the EScribe software) reading and from thermocouples attached to the coils during simulated puffing conditions. In addition, aerosol temperatures were measured inside the atomizer and at the mouthpiece., Results: Measured temperatures varied widely across samples taken from the same brand. For example, thermocouple measurements for one unit were 40 Celsius (°C) below the 300 °C set point, while another unit of the same brand exceeded the set point by more than 100 °C. We observed a significant variation in temperature (approximately 100 °C) along the length of the coil in some cases., Conclusions: The possibility of wide temperature variation across ENDS samples, as well as variations between maximum coil temperatures and internal temperature readings, may have implications for studies that seek to determine correlations between coil temperature and toxin generation., Competing Interests: The authors have declared that no competing interests exist.

Background: Changes in connector design for the gastrostomy tube were implemented to reduce the risk of misconnections. This study aimed to determine whether there are differences in gravity flow rates between legacy devices and the ENFit devices intended to replace them., Materials and Methods: We compared 5 legacy gastrostomy tube brands with 3 corresponding ENFit brands, sized between 14 French (Fr) and 24 Fr. Seven commercial diets were used. One comparison involved low-profile devices., Results: Whether an ENFit device manifested a lower flow rate than a legacy device was not a strong function of diet. One 14-Fr ENFit device, because of its reduced distal inner tube diameter, produced an average feeding time of 56 (±13) minutes from a 20-minute baseline. For other 14-Fr ENFit devices, the increase was much less pronounced (25 ± 4 minutes). At larger sizes, both decreases and increases in feeding time were observed, depending on device type; on average, the 20-minute feeding time increased to 25 (±7) minutes. For low-profile devices, across all sizes, an increase in 20-minute feeding time occurred, but the difference was small (23 ± 2)., Conclusion: Statistically lower flow rates were observed for 70% of ENFit devices relative to their legacy counterparts. We estimate that 30% of the differences may be noticeable. In the scenarios studied, lower flow rates (relative to other devices at the same Fr number) arise from energy losses in straight tubing. This difference can be reduced by increasing the tube inner diameters in distal end of ENFit tubes., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Long procedure times and collateral damage remain challenges in high-intensity focused ultrasound (HIFU) medical procedures. Magnetic nanoparticles (mNPs) and gold nanoparticles (gNPs) have the potential to reduce the acoustic intensity and/or exposure time required in these procedures. In this research, we investigated relative advantages of using gNPs and mNPs during HIFU thermal-ablation procedures. Tissue-mimicking phantoms containing embedded thermocouples (TCs) and physiologically acceptable concentrations (0.0625% and 0.125%) of gNPs were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 s. It was observed that when the concentration of gNPs was doubled from 0.0625% to 0.125%, the temperature rise increased by 80% for a power of 5.2 W. For a fixed concentration (0.0625%), the energy absorption was 1.7 times greater for mNPs than gNPs for a power of 5.2 W. Also, for the power of 14.5 W, the sonication time required to generate a lesion volume of 50 mm3 decreased by 1.4 times using mNPs, compared with gNPs, at a concentration of 0.0625%. We conclude that mNPs are more likely than gNPs to produce a thermal enhancement in HIFU ablation procedures.

Objective: We aim to demonstrate the in vivo capability of a wearable sensor technology to detect localized perturbations of sensory-evoked brain activity., Methods: Cortical somatosensory evoked potentials (SSEPs) were recorded in mice via wearable, flexible epidermal electrode arrays. We then utilized the sensors to explore the effects of transcranial focused ultrasound, which noninvasively induced neural perturbation. SSEPs recorded with flexible epidermal sensors were quantified and benchmarked against those recorded with invasive epidural electrodes., Results: We found that cortical SSEPs recorded by flexible epidermal sensors were stimulus frequency dependent. Immediately following controlled, focal ultrasound perturbation, the sensors detected significant SSEP modulation, which consisted of dynamic amplitude decreases and altered stimulus-frequency dependence. These modifications were also dependent on the ultrasound perturbation dosage. The effects were consistent with those recorded with invasive electrodes, albeit with roughly one order of magnitude lower signal-to-noise ratio., Conclusion: We found that flexible epidermal sensors reported multiple SSEP parameters that were sensitive to focused ultrasound. This work therefore 1) establishes that epidermal electrodes are appropriate for monitoring the integrity of major CNS functionalities through SSEP; and 2) leveraged this technology to explore ultrasound-induced neuromodulation. The sensor technology is well suited for this application because the sensor electrical properties are uninfluenced by direct exposure to ultrasound irradiation., Significance: The sensors and experimental paradigm we present involve standard, safe clinical neurological assessment methods and are thus applicable to a wide range of future translational studies in humans with any manner of health condition.

Respiratory protective devices (RPDs) are critical for reducing the spread of infection via inhalable droplets. In determining the type of RPD to deploy, it is important to know the reduction in the infection rate that the RPD enables for the given pathogen and population. This paper extends a previously developed susceptible-infected-recovered (SIR) epidemic model to analyse the effect of a protection strategy. An approximate solution to the modified SIR equations, which compares well with a full numerical solution to the equations, was used to derive a simple threshold equation for predicting when growth of the infected population will occur for a given protection strategy. The threshold equation is cast in terms of a generalized reproduction number, which contains the characteristics of the RPDs deployed by the susceptible and infected populations, as well as the degree of compliance in wearing the equipment by both populations. An example calculation showed that with 50% of the susceptible population deploying RPDs that transmit 15% of pathogens, and an unprotected infected population, an otherwise growing infection rate can be converted to one that decays. When the infected population deploys RPDs, the transmission rate for the RPDs worn by the susceptible population can be higher.

The presence of hydrated salts on Mars indicates that some regions of its surface might be habitable if suitable metabolizable substrates are available. However, several lines of evidence have shown that Mars' regolith contains only trace levels of the organic matter needed to support heterotrophic microbes. Due to the scarcity of organic carbon, carbon monoxide (CO) at a concentration of about 700 parts per million (about 0.4 Pa) might be the single most abundant readily available substrate that could support near-surface bacterial activity. Although a variety of electron acceptors can be coupled to CO oxidation, perchlorate is likely the most abundant potential oxidant in Mars' brines. Whether perchlorate, a potent chaotrope, can support microbial CO oxidation has not been previously documented. We report here the first evidence for perchlorate-coupled CO oxidation based on assays with two distinct euryarchaeal extreme halophiles. CO oxidation occurred readily in 3.8 M NaCl brines with perchlorate concentrations from 0.01 to 1 M. Both isolates were able to couple CO with perchlorate or chlorate under anaerobic conditions with or without nitrate as an inducer for nitrate reductase, which serves as a perchlorate reductase in extreme halophiles. In the presence of perchlorate, CO concentrations were reduced to levels well below those found in Mars' atmosphere. This indicates that CO could contribute to the survival of microbial populations in hydrated salt formations or brines if water activities are suitably permissive.

A "credible" computational fluid dynamics (CFD) model has the potential to provide a meaningful evaluation of safety in medical devices. One major challenge in establishing "model credibility" is to determine the required degree of similarity between the model and experimental results for the model to be considered sufficiently validated. This study proposes a "threshold-based" validation approach that provides a well-defined acceptance criteria, which is a function of how close the simulation and experimental results are to the safety threshold, for establishing the model validity. The validation criteria developed following the threshold approach is not only a function of Comparison Error, E (which is the difference between experiments and simulations) but also takes in to account the risk to patient safety because of E. The method is applicable for scenarios in which a safety threshold can be clearly defined (e.g., the viscous shear-stress threshold for hemolysis in blood contacting devices). The applicability of the new validation approach was tested on the FDA nozzle geometry. The context of use (COU) was to evaluate if the instantaneous viscous shear stress in the nozzle geometry at Reynolds numbers (Re) of 3500 and 6500 was below the commonly accepted threshold for hemolysis. The CFD results ("S") of velocity and viscous shear stress were compared with inter-laboratory experimental measurements ("D"). The uncertainties in the CFD and experimental results due to input parameter uncertainties were quantified following the ASME V&V 20 standard. The CFD models for both Re = 3500 and 6500 could not be sufficiently validated by performing a direct comparison between CFD and experimental results using the Student's t-test. However, following the threshold-based approach, a Student's t-test comparing |S-D| and |Threshold-S| showed that relative to the threshold, the CFD and experimental datasets for Re = 3500 were statistically similar and the model could be considered sufficiently validated for the COU. However, for Re = 6500, at certain locations where the shear stress is close the hemolysis threshold, the CFD model could not be considered sufficiently validated for the COU. Our analysis showed that the model could be sufficiently validated either by reducing the uncertainties in experiments, simulations, and the threshold or by increasing the sample size for the experiments and simulations. The threshold approach can be applied to all types of computational models and provides an objective way of determining model credibility and for evaluating medical devices.

High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm 3 was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.

Collateral damage and long sonication times occurring during high-intensity focused ultrasound (HIFU) ablation procedures limit clinical advancement. In this reserarch, we investigated whether the use of magnetic nano-particles (mNPs) can reduce the power required to ablate tissue or, for the same power, reduce the duration of the procedure. Tissue-mimicking phantoms containing embedded thermocouples and physiologically acceptable concentrations (0%, 0.0047%, and 0.047%) of mNPs were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 seconds. Lesion volumes were determined for the phantoms with and without mNPs. It was found that with the 0.047% mNP concentration, the power required to obtain a lesion volume of 13 mm3 can be halved, and the time required to achieve a 21 mm3 lesion decreased by a factor of 5. We conclude that mNPs have the potential to reduce damage to healthy tissue, and reduce the procedure time, during tumor ablation using HIFU.

The efficacy of a new spot-on formulation of selamectin/sarolaner was evaluated against induced Otodectes cynotis infestations in cats in two randomized, blinded studies. Fourteen and 16 cats were randomly assigned to treatment groups in Studies 1 and 2, respectively. On Day 0, animals were either treated with placebo or with the spot-on formulation at the minimal dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight. Treatments were administered topically at the base of the neck. Presence of live mites was evaluated 14days after treatment administration by otoscopic examination and total live mite counts (adults plus immature) were conducted on Day 30 by ear lavage. Efficacy was calculated based on the reduction of mean total live mite counts on Day 30 in the selamectin/sarolaner-treated group versus the placebo-treated group. There were no treatment-related adverse reactions during the studies, apart from one cat in each treatment group with alopecia at the administration site. In both studies combined, live mites were present on Day 14, in 14 out of 15 cats in the placebo-treated groups and in 2 out of 15 cats in the selamectin/sarolaner-treated groups. On Day 30, the arithmetic mean live mite counts were 576.9 and 875.8 in the placebo-treated groups and 5.8 and 4.7 in the selamectin/sarolaner-treated groups, in Studies 1 and 2, respectively. The live mite counts were significantly (P≤0.0021) lower in the selamectin/sarolaner-treated groups compared to the placebo-treated groups with efficacies of 99.2% and 99.3%, in Studies 1 and 2 respectively. A single administration of a new spot-on formulation of selamectin/sarolaner at the minimum dose was safe and highly efficacious in the treatment of ear mite infestations in cats., (Copyright © 2017 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

Background: Safety analyses of transcranial therapeutic ultrasound procedures require knowledge of the dependence of the rupture probability and rupture time upon sonication parameters. As previous vessel-rupture studies have concentrated on a specific set of exposure conditions, there is a need for more comprehensive parametric studies., Methods: Probability of rupture and rupture times were measured by exposing the large blood vessel of a live earthworm to high-intensity focused ultrasound pulse trains of various characteristics. Pressures generated by the ultrasound transducers were estimated through numerical solutions to the KZK (Khokhlov-Zabolotskaya-Kuznetsov) equation. Three ultrasound frequencies (1.1, 2.5, and 3.3 MHz) were considered, as were three pulse repetition frequencies (1, 3, and 10 Hz), and two duty factors (0.0001, 0.001). The pressures produced ranged from 4 to 18 MPa. Exposures of up to 10 min in duration were employed. Trials were repeated an average of 11 times., Results: No trends as a function of pulse repetition rate were identifiable, for either probability of rupture or rupture time. Rupture time was found to be a strong function of duty factor at the lower pressures; at 1.1 MHz the rupture time was an order of magnitude lower for the 0.001 duty factor than the 0.0001. At moderate pressures, the difference between the duty factors was less, and there was essentially no difference between duty factors at the highest pressure. Probability of rupture was not found to be a strong function of duty factor. Rupture thresholds were about 4 MPa for the 1.1 MHz frequency, 7 MPa at 3.3 MHz, and 11 MPa for the 2.5 MHz, though the pressure value at 2.5 MHz frequency will likely be reduced when steep-angle corrections are accounted for in the KZK model used to estimate pressures. Mechanical index provided a better collapse of the data (less separation of the curves pertaining to the different frequencies) than peak negative pressure, for both probability of rupture and rupture time., Conclusion: The results provide a database with which investigations in more complex animal models can be compared, potentially establishing trends by which bioeffects in human vessels can be estimated.

Surgical respirators, surgical masks (SMs), and facemasks for pediatric use (FPUs) are routinely used in the U.S. healthcare industry as personal protective equipment (PPE) against infectious diseases. While N95s including surgical respirators have been routinely studied, SMs and FPUs have not received as much attention, particularly in the context of aerosolized threats. This is because SMs and PFUs are not designed to protect against sub-micron aerosols. However, with the possibility of new or re-emerging airborne diseases or bio-aerosol weapons lingering, combined with the limited availability of respirators and logistical issues associated with fit-testing millions, the general adult and pediatric populations may elect to wear SMs and FPUs, respectively, in the case of a pandemic or a bio-terrorist attack. When a person dons a PPE, gaps are created between the wearer's face and the PPE, and aerosols leaking through these gaps can be an important contributor to the risk of infection compared to filtered aerosols. To understand and quantify the contribution of leakage of aerosols through gaps, with particular emphasis on SMs and FPUs, this study investigated leakage of charge-neutralized, polydispersed, dried sodium-chloride aerosols across different brands of PPE. Different breathing rates, aerosol particle sizes, and gap sizes were considered. A few major findings of this study were: (a) leakage, is not a strong function of sub-micron aerosol size; (b) for the same gap size, leakage of aerosols through surgical respirators can often be higher than in SMs and FPUs; and (c) as the gap size increases, the increase in leakage through surgical respirators is higher compared for SMs and FPUs, implying that some SMs and FPUs that possess electret layers may be preferable to N95s that have not been fit-tested. The results obtained can also be used to explain conflicting findings from clinical studies on the effectiveness of SMs when compared to N95s and can be input into risk-assessment models to determine the increase in infection rate resulting from deployment of PPE under less-than-ideal conditions.

A novel member of Acidobacteria was isolated from a microbial mat growing on a geothermally heated dead tree trunk in Hawai'i Volcanoes National Park (HI, USA). The rod-shaped, Gram-negative capsulated cells of strain PMMR2T were non-motile and catalase and oxidase negative. Growth occurred aerobically from 15 to 55 °C (optimum, 40 °C) and at pH values from 4.5 to 7.0 (optimum, 6.5). A limited range of sugars and organic acids supported growth. However, results of a genomic analysis suggested that various polysaccharides might be hydrolysed as carbon sources, and evidence for pectin degradation was observed in liquid cultures. A genomic analysis also revealed genes for a Group 1f uptake hydrogenase; assays with liquid cultures confirmed hydrogen consumption, including uptake at sub-atmospheric concentrations. Nitrate was not dissimilated to nitrite. Major membrane fatty acids included iso-C15 : 0 and iso-C17 : 0. The G+C content was 57.2mol%. A comparative genome analysis revealed an average nucleotide identity of 72.2 % between PMMR2T and its nearest cultured phylogenetic neighbour, Acidobacterium capsulatum ATCC 51196T (=JCM 7670T); analysis of the 16S rRNA gene revealed a 96.8 % sequence identity with Acidobacterium capsulatum ATCC 51196T. These results and other phenotypic differences indicated that strain PMMR2T represents a novel species in the genus Acidobacterium, for which the name Acidobacterium ailaaui sp. nov. is proposed. The type strain, PMMR2T (=DSM 27394T=LMG 28340T), is the second formal addition to the genus Acidobacterium.

Rapid detection and diagnosis of a traumatic brain injury (TBI) can significantly improve the prognosis for recovery. Helmet-mounted sensors that detect impact severity based on measurements of acceleration or pressure show promise for aiding triage and transport decisions in active, field environments such as professional sports or military combat. The detected signals, however, report on the mechanics of an impact rather than directly indicating the presence and severity of an injury. We explored the use of cortical somatosensory evoked electroencephalographic potentials (SSEPs) to detect and track, in real-time, neural electrophysiological abnormalities within the first hour following head injury in an animal model. To study the immediate electrophysiological effects of injury in vivo, we developed an experimental paradigm involving focused ultrasound that permits continuous, real-time measurements and minimizes mechanical artifact. Injury was associated with a dramatic reduction of amplitude over the damaged hemisphere directly after the injury. The amplitude systematically improved over time but remained significantly decreased at one hour, compared with baseline. In contrast, at one hour there was a concomitant enhancement of the cortical SSEP amplitude evoked from the uninjured hemisphere. Analysis of the inter-trial electroencephalogram (EEG) also revealed significant changes in low-frequency components and an increase in EEG entropy up to 30 minutes after injury, likely reflecting altered EEG reactivity to somatosensory stimuli. Injury-induced alterations in SSEPs were also observed using noninvasive epidermal electrodes, demonstrating viability of practical implementation. These results suggest cortical SSEPs recorded at just a few locations by head-mounted sensors and associated multiparametric analyses could potentially be used to rapidly detect and monitor brain injury in settings that normally present significant levels of mechanical and electrical noise.

Scant evidence exists in the literature for best practices in training assertive community treatment (ACT) teams to deliver highly effective services to consumers. This column describes a blended training curriculum, which includes both face-to-face and distance learning strategies, developed by the ACT Training Institute in New York State to meet the ongoing training needs of teams across New York State. Data on training uptake, which has steadily increased over time, are reported. The role of the state is crucial in driving adoption of training activities. The column also describes how the ACT Training Institute uses fidelity and outcome data to identify training needs.

Background: The lone star tick, Amblyomma americanum, infests dogs and cats in North America and transmits the pathogens Ehrlichia chaffeensis and Ehrlichia ewingii, which cause monocytic and granulocytic ehrlichiosis in dogs and humans, and Cytauxzoon felis which causes cytauxzoonosis in cats. A parasiticide's speed of kill is important to minimize the direct deleterious effects [related to blood-feeding] of tick infestation and reduce the risk of transmission of tick-borne pathogens. In this study the speed of kill of sarolaner (Simparica™ Chewables) administered monthly for 3 months against A. americanum on dogs was evaluated and compared with a single dose of fluralaner (Bravecto(®)) for 13 weeks., Methods: Based on pretreatment tick counts, 24 dogs were randomly allocated to treatment with placebo or sarolaner at the label rate (2 to 4 mg/kg) on Days 0, 30 and 60 or with fluralaner (25 to 56 mg/kg) once according to manufacturer's instructions on Day 0. Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 14, 28, 42, 58, 76 and 90. Acaricidal efficacy was determined at each time point relative to counts for placebo dogs., Results: Monthly oral doses of sarolaner provided > 95 % efficacy within 24 h of treatment, and consistently provided > 70 % efficacy against subsequent re-infestations with ticks within 24 h over the entire treatment period. Significantly more live ticks were recovered from fluralaner-treated dogs than from sarolaner-treated dogs at 24 h after re-infestation from Day 42 onwards. At 24 h, efficacy of fluralaner was ≤ 20 % from Day 42 to the end of the study on Day 90. There were no adverse reactions to treatment., Conclusions: In this controlled laboratory evaluation, monthly treatment with sarolaner provided consistent efficacy against A. americanum with > 70 % of ticks killed within 24 h after a single oral dose over the duration of the study. Monthly treatment with sarolaner consistently killed significantly more ticks within 24 h than a single dose of fluralaner from 6 weeks after initial treatment.

The rapid speed of kill of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was demonstrated against three tick species known to infest dogs in Europe or the United States. Efficacy was measured against an existing infestation and against subsequent weekly re-infestations for 35 days after treatment. Dogs were randomly allocated to treatment with a single oral dose of either placebo or sarolaner (2mg/kg) based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Ixodes scapularis, Ixodes ricinus or Amblyomma maculatum ticks on Days-2, 7, 14, 21, 28 and 35. Tick counts were conducted at 4 (I. scapularis only), 8, 12 and 24h after treatment on Day 0 and after each subsequent re-infestation. No treatment-related adverse reactions occurred during any of these studies. Dogs in the placebo-treated groups maintained adequate tick infestations (recovery of 20-70% of applied ticks) throughout the duration of the studies. Following treatment, live tick counts were significantly reduced relative to placebo at the 8h post treatment counts indicating that sarolaner started killing existing infestations of ticks rapidly after treatment. Efficacy was 90.1% against I. ricinus, 98.8% against I. scapularis, and 99.2% against A. maculatum within 12h, and 100% efficacy was achieved at 24h after treatment against all three tick species. This speed of kill was maintained throughout the month with ≥95.7%, ≥98.7% and ≥89.6% efficacy against I. scapularis, I. ricinus, and A. maculatum, respectively, at 24h after re-infestation at least through Day 28., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Three laboratory studies were conducted to determine the appropriate dose of sarolaner, a novel isoxazoline, for the treatment and month-long control of infestations of fleas and ticks on dogs. In the first study, dogs were treated orally with sarolaner suspension formulations at 1.25, 2.5 or 5.0mg/kg, and infested with Dermacentor reticulatus, Rhipicephalus sanguineus ticks and with Ctenocephalides felis felis (cat flea) prior to treatment and then weekly for up to 8 weeks. Fleas and ticks were counted 48h after treatment and after each subsequent infestation at 24h for fleas and 48h for ticks. The lowest dose of sarolaner (1.25mg/kg) provided 100% efficacy against fleas from treatment through Day 35 and 98.4% at Day 56. This dose of sarolaner resulted in 99.7-100% control of both species of ticks through Day 28. In Study 2, dogs were dosed orally with placebo or sarolaner suspension formulations at 0.625, 1.25 or 2.5mg/kg and infested with Ixodes scapularis prior to treatment and weekly for 6 weeks, Amblyomma americanum (pretreatment and Day 26), Dermacentor variabilis (Day 33) and A. maculatum (Day 41). Ixodes scapularis was the most susceptible; the lowest dose (0.625mg/kg) providing>95% efficacy through Day 43. Efficacy against D. variabilis on Day 35 was>95% at 1.25 and 2.5mg/kg, whereas the 0.625mg/kg dose gave only 61.4% efficacy. Amblyomma spp. were the least susceptible ticks; efficacy of the 1.25mg/kg dose at Day 28 for A. americanum was markedly lower (88.5%) than achieved for D. reticulatus (100%) at Day 28 and also lower than for D. variabilis at Day 35 (96.2%). In Study 3, dogs were dosed orally with placebo or sarolaner in the proposed commercial tablet (Simparica™) at 1.0, 2.0 or 4.0mg/kg, and infested with A. maculatum, one of the ticks determined to be dose limiting, prior to treatment and then weekly for 5 weeks. All doses gave 100% control of the existing infestation. The two highest dosages resulted in >93% control of subsequent challenges for 5 weeks. There was no significant improvement in efficacy provided by the 4.0 mg/kg dose over the 2.0mg/kg dose (P>0.05) at any time point. The 2.0mg/kg dose was superior to the 1.0mg/kg on Day 14 (P=0.0086) and as efficacy for 1.0mg/kg declined below 90% at Day 28, a single 1mg/kg dose would not provide a full month of tick control. Thus, 2.0mg/kg was selected as the sarolaner dose rate to provide flea and tick control for at least one month following a single oral treatment., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The efficacy of sarolaner (Simparica™, Zoetis) was evaluated against Demodex spp. in dogs with generalized demodicosis and against Otodectes cynotis (otodectic mange) in dogs with induced infestations. In the first study, 16 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites were randomly assigned to treatment with either sarolaner (2mg/kg) orally on Days 0, 30 and 60, or topical imidacloprid (10mg/kg) plus moxidectin (2.5mg/kg) solution every 7 days from Day 0 to Day 81. For sarolaner-treated dogs, pretreatment mite counts were reduced by 97.1% at 14days and 99.8% by 29 days after the first dose, with no live mites detected thereafter. Weekly imidacloprid plus moxidectin resulted in 84.4 and 95.6% reduction at these two time points, respectively, with no mites detected from Day 74 on. All dogs in both groups showed marked improvement in the clinical signs of demodicosis. In the second study, 32 dogs with induced infestations of O. cynotis were randomly assigned (eight per group) to oral sarolaner (2mg/kg) as a single treatment on Day 0 or as a two dose regime (Days 0 and 30), or a placebo group for each of the dose regimes. Sarolaner administered at 2mg/kg as a single oral dose resulted in a 98.2% reduction at Day 30 and two doses of sarolaner, administered one month apart, resulted in a 99.5% reduction in ear mites at Day 60 compared to placebo controls. There were no treatment related adverse events in either study. In these studies, sarolaner at an oral dose of 2mg/kg was highly effective in reducing the live mite counts associated with a natural infestation of Demodex spp. and an induced infestation of O. cynotis. In addition, the Demodex-infested dogs showed a marked improvement in the clinical signs of generalized demodicosis., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The efficacy of a single oral dose of a novel isoxazoline, sarolaner (Simparica™, Zoetis), for the treatment and control of flea infestations on dogs was confirmed in five laboratory studies. The studies were conducted using adult purpose-bred Beagles and/or mixed breed dogs. All animals were individually identified and housed, and were allocated randomly to treatment with either placebo or sarolaner (eight to 10 per group) based on pretreatment parasite counts. Three studies used cat flea (Ctenocephalides felis felis) strains recently isolated from the field from the US, EU, or Australia; in the fourth study a laboratory strain (KS1) with documented tolerance to a number of insecticides such as fipronil, imidacloprid, and permethrin was used. In the fifth study, dogs were infested with dog fleas, Ctenocephalides canis. Dogs were treated orally on Day 0 with a placebo or a sarolaner tablet providing a minimum dose of 2mg/kg. Dogs were infested with approximately 100 unfed, adult fleas prior to treatment and at weekly intervals post-treatment. Comb counts were conducted to determine the numbers of viable fleas at 24h after treatment and after each subsequent infestation. Efficacy against C. felis and C. canis was 99.8-100% from treatment through Day 35. In all five studies, elimination of existing infestations was achieved within 24h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24h after infestation throughout the 35day study periods, with only single live C. felis found on two dogs on Day 28 in one study, and on a single dog on Day 35 in another study. There were no adverse reactions to treatment with sarolaner. These studies confirmed that a single oral dose of sarolaner at 2mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Four studies were conducted to evaluate the speed of kill, effect on egg production, and efficacy in a simulated infested-home environment of a novel isoxazoline, sarolaner (Simparica™, Zoetis), against fleas on dogs. Individually identified and housed, purpose-bred Beagles were used in each study and were allocated randomly to groups based on pretreatment parasite counts. In two speed of kill studies, groups of dogs infested with 100 fleas prior to treatment were treated orally with placebo or sarolaner tablets providing the minimum dose of 2mg/kg and then re-infested with fleas weekly for five weeks post-treatment. Comb counts were conducted to determine the numbers of viable fleas at one to three, four, eight and 12h after treatment and each subsequent infestation. In the egg production study, sarolaner- and placebo-treated dogs were similarly challenged with fleas and at 48h after each infestation the dogs were housed for 20h in cages allowing the collection and counting of all flea eggs produced during this period. Collected eggs were incubated to evaluate hatch and development to adults. The last study used dogs housed in a flea-infested simulated-home environment. Dogs were allocated to treatment with either placebo or sarolaner tablets providing a dose of 2mg/kg once a month for three treatments. Flea infestations were assessed by comb counts (fleas were replaced on the dogs) on Days 14, 30, 44, 60, 74 and 90. The speed of kill studies demonstrated that a single 2mg/kg oral dose of sarolaner started killing fleas within three to four hours after treatment or subsequent re-infestations for up to a month, and achieved ≥98% control of fleas by eight hours after treatment or re-infestation for 28 days. In the study to assess effects on flea reproduction, a single oral treatment of sarolaner resulted in the complete cessation of egg-laying for 35 days. This rapid kill of fleas and inhibition of reproduction were confirmed in a simulated-home environment where the existing infestations were reduced by >95% within two weeks of the first treatment and eliminated from the dogs after two monthly doses., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The efficacy of a single oral treatment with sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against five tick species known to infest dogs in the United States. A total of 10 laboratory studies, two against each species, were conducted using adult purpose-bred mongrels or Beagle dogs. In each study, 16 dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis or Rhipicephalus sanguineus ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated with a placebo or a sarolaner tablet providing a minimum dose of 2 mg/kg. Tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions during any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly lower (P≤0.0001) in the sarolaner-treated group compared to the tick counts in the placebo group at all timepoints. Treatment with sarolaner resulted in ≥99.6% efficacy against existing infestations of all five tick species within 48h. The efficacy against weekly post-treatment re-infestations of all tick species was ≥96.9% for at least 35 days after treatment. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2mg/kg, resulted in excellent efficacy within 48h against existing tick infestations, and against weekly re-infestations for 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide rapid treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in the US., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

A technique useful for performing derating at acoustic powers where significant harmonic generation occurs is illustrated and validated with experimental measurements. The technique was previously presented using data from simulations. The method is based upon a Gaussian representation of the propagation modes, resulting in simple expressions for the modal quantities, but a Gaussian source is not required. The nonlinear interaction of modes within tissue is estimated from the nonlinear interaction in water, using appropriate amounts of source reduction and focal-point reduction derived from numerical simulations. An important feature of this nonlinear derating method is that focal temperatures can be estimated with little additional effort beyond that required to determine the focal pressure waveforms. Hydrophone measurements made in water were used to inform the derating algorithm, and the resulting pressure waveforms and increases in temperature were compared with values directly measured in tissue phantoms. For a 1.05 MHz focused transducer operated at 80 W and 128 W, the derated pressures (peak positive, peak negative) agreed with the directly measured values to within 11%. Focal temperature rises determined by the derating method agreed with values measured using a remote thermocouple technique with a difference of 17%.

The phylogenetic affiliations of organisms responsible for aerobic CO oxidation in hypersaline soils and sediments were assessed using media containing 3.8 M NaCl. CO-oxidizing strains of the euryarchaeotes, Haloarcula, Halorubrum, Haloterrigena and Natronorubrum, were isolated from the Bonneville Salt Flats (UT) and Atacama Desert salterns (Chile). A halophilic euryarchaeote, Haloferax strain Mke2.3(T), was isolated from Hawai'i Island saline cinders. Haloferax strain Mke2.3(T) was most closely related to Haloferax larsenii JCM 13917(T) (97.0% 16S rRNA sequence identity). It grew with a limited range of substrates, and oxidized CO at a headspace concentration of 0.1%. However, it did not grow with CO as a sole carbon and energy source. Its ability to oxidize CO, its polar lipid composition, substrate utilization and numerous other traits distinguished it from H. larsenii JCM 13917(T), and supported designation of the novel isolate as Haloferax namakaokahaiae Mke2.3(T), sp. nov (= DSM 29988, = LMG 29162). CO oxidation was also documented for 'Natronorubrum thiooxidans' HG1 (Sorokin, Tourova and Muyzer 2005), N. bangense (Xu, Zhou and Tian 1999) and N. sulfidifaciens AD2(T) (Cui et al. 2007). Collectively, these results established a previously unsuspected capacity for extremely halophilic aerobic CO oxidation, and indicated that the trait might be widespread among the Halobacteriaceae, and occur in a wide range of hypersaline habitats., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Fleas are a ubiquitous ectoparasite infesting dogs and cause direct discomfort, allergic reactions and are responsible for the transmission of several pathogens. The rapid speed of kill of a parasiticide is important to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with spinosad in combination with milbemycin oxime (Trifexis) for 5 weeks after a single oral dose., Methods: Twenty-four dogs were randomly allocated to treatment with a single oral dose per product label of sarolaner (2 to 4 mg/kg), spinosad/milbemycin oxime (30 to 60 mg/kg / 0.2 to 0.4 mg/kg), or placebo based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy (reduction in live flea counts) of each treatment was determined at each time point relative to counts for placebo dogs., Results: There were no adverse reactions to treatment. A single oral dose of sarolaner provided ≥94.0 % efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were eradicated from all dogs and they remained flea free at 24 h. Significantly greater numbers of live fleas were recovered from spinosad/milbemycin oxime-treated dogs at 8 h from Day 21 to Day 35 (P ≤ 0.0085), and at 12 and 24 h on Day 35 (P ≤ 0.0002)., Conclusions: In this controlled laboratory evaluation, dogs treated with sarolaner had significantly fewer live fleas than spinosad/milbemycin oxime- treated dogs at 8 h after re-infestation from Day 21 after a single oral dose. The rapid and consistent kill of fleas after a single oral dose of sarolaner over 35 days indicates that this treatment should provide highly effective control of flea infestations, relief for dogs afflicted with flea allergy dermatitis, and also reduce the risk of transmission of flea-borne pathogens.

Background: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs and cats in North America and is the main vector for the pathogen that causes Lyme disease in dogs and humans. The speed of kill of a parasiticide is critical to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of tick-borne pathogen transmission. In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica), against I. scapularis on dogs was evaluated and compared with afoxolaner (NexGard) for five weeks after a single oral dose., Methods: Twenty four dogs were randomly allocated to treatment with either placebo, sarolaner (2 to 4 mg/kg), or afoxolaner (2.5 to 6.8 mg/kg) based on pretreatment tick counts. Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs., Results: A single oral dose of sarolaner provided >99% efficacy within 24 h of treatment and >95% against subsequent weekly re-infestations of ticks consistently to Day 35. For the earlier time points, sarolaner significantly reduced tick counts versus placebo from Day 0 to Day 21 at 8 and 12 h, and on Day 35 at 12 h (P ≤ 0.0174), while afoxolaner was only significantly lower at 8 h on Days 0 and 14 (P ≤ 0.0309), and at 12 h on Day 0 only (P < 0.0001). Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 24 h after infestation from Day 14 to Day 35 (P ≤ 0.0278). At 24 h, efficacy (based on geometric mean counts) of afoxolaner declined to less than 80% from Day 21 through the end of the study, while efficacy for sarolaner was >95% for 35 days. There were no adverse reactions to treatments., Conclusions: In this controlled laboratory evaluation, sarolaner had a faster speed of kill against I. scapularis than afoxolaner. This was noticeably more pronounced towards the end of the monthly treatment period. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and re-infestation over 35 days suggests this treatment will provide highly effective and reliable control of ticks over the entire treatment interval, and should reduce the risk of tick-borne diseases, including Lyme disease whose agent is vectored by I. scapularis.

As part of an ongoing effort to develop verification and validation (V&V) standards for using computational fluid dynamics (CFD) in the evaluation of medical devices, we have developed idealized flow-based verification benchmarks to assess the implementation of commonly cited power-law based hemolysis models in CFD. Verification process ensures that all governing equations are solved correctly and the model is free of user and numerical errors. To perform verification for power-law based hemolysis modeling, analytical solutions for the Eulerian power-law blood damage model (which estimates hemolysis index (HI) as a function of shear stress and exposure time) were obtained for Couette and inclined Couette flow models, and for Newtonian and non-Newtonian pipe flow models. Subsequently, CFD simulations of fluid flow and HI were performed using Eulerian and three different Lagrangian-based hemolysis models and compared with the analytical solutions. For all the geometries, the blood damage results from the Eulerian-based CFD simulations matched the Eulerian analytical solutions within ∼1%, which indicates successful implementation of the Eulerian hemolysis model. Agreement between the Lagrangian and Eulerian models depended upon the choice of the hemolysis power-law constants. For the commonly used values of power-law constants (α  = 1.9-2.42 and β  = 0.65-0.80), in the absence of flow acceleration, most of the Lagrangian models matched the Eulerian results within 5%. In the presence of flow acceleration (inclined Couette flow), moderate differences (∼10%) were observed between the Lagrangian and Eulerian models. This difference increased to greater than 100% as the beta exponent decreased. These simplified flow problems can be used as standard benchmarks for verifying the implementation of blood damage predictive models in commercial and open-source CFD codes. The current study only used power-law model as an illustrative example to emphasize the need for model verification. Similar verification problems could be developed for other types of hemolysis models (such as strain-based and energy dissipation-based methods). However, since the current study did not include experimental validation, the results from the verified models do not guarantee accurate hemolysis predictions. This verification step must be followed by experimental validation before the hemolysis models can be used for actual device safety evaluations.

Background: In the event of a public-health threat involving bioaerosols, such as a terrorist attack or pandemic, options for devices to protect the pediatric population are limited. One strategy involves deployment of facemasks meant for the pediatric population, although protection against bioaerosols was not an intended use of such masks and little is known about their effectiveness., Methods: We chose 3 brands of facemasks for pediatric use for characterizing penetration. To validate our experimental technique, 2 N95 respirator brands were also tested. All barriers were subjected to neutralized polydispersed sodium chloride aerosols, and their intrinsic penetration was evaluated in the submicron size range at different flow rates., Results: As expected, the N95 brands had low penetration (5% or less) at the highest flow rates. However, for the facemasks for pediatric use, penetration varied significantly amongst brands at the highest flow rates (~15%->50%). Studies with isopropanol-dipped respirators and facemasks demonstrated that not all brands of facemasks for pediatric use have electret layers., Conclusions: Our bench tests suggest that the intrinsic penetration through facemasks for pediatric use can be high in the submicron size range. These data can be used in risk-assessment models to determine the extent to which facemasks for pediatric use reduce the likelihood of infection in emergency situations., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.)

This column focuses on use of learning collaboratives by the Center for Practice Innovations to help programs implement the evidence-based individual placement and support model of supported employment in New York State. These learning collaboratives use fidelity and performance indicator data to drive the development of program-specific individualized quality improvement plans. As of 2014, 59 (69%) of 86 eligible programs have joined the initiative. Programs are achieving employment outcomes for consumers on par with national benchmarks, along with improved fidelity.