bluuebunny/crossref_metadata_2025 huggingface dataset:
The novel long noncoding RNA CRART16 confers cetuximab resistance in colorectal cancer cells by enhancing ERBB3 expression via miR-371a-5p
Authors: Zhang Xiaoqian , Wen Long , Chen Shanwen , Zhang Junling , Ma Yongchen , Hu Jianwen , Yue Taohua , Wang Jingui , Zhu Jing , Bu Dingfang , Wang Xin
Published: March 2020

Background

Long noncoding RNAs (lncRNAs) have been shown to participate in multiple biological processes and confer drug resistance. However, it remains unclear whether lncRNAs are involved in conferring cetuximab resistance in colorectal cancer (CRC) cells.

Methods

Cell Counting Kit-8 (CCK-8) assays were performed to assess the sensitivity of CRC cell lines to cetuximab treatment. We incubated Caco-2 cells, which are partially responsive to cetuximab, with increasing concentrations of cetuximab for approximately 6 months to generate Caco-2 cetuximab-resistant (Caco-2 CR) cells. Microarray analysis comparing Caco-2 CR with Caco-2 cells was used to identify lncRNAs that were potentially related to cetuximab resistance. Caco-2 cells were stably transduced with cetuximab resistance-associated RNA transcript 16 (CRART16) or an empty vector using lentiviral infection; the cells were designated Caco-2-CRART16 and Caco-2-NC, respectively, and were analyzed with RNA sequencing (RNA-seq). Quantitative real-time PCR (qRT-PCR) was performed to investigate RNA expression. Flow cytometry and TUNEL assays were used to assess apoptosis levels induced by cetuximab. The cell cycle, stemness biomarkers and membrane proteins of CRC cells were assessed via flow cytometry. RNA fluorescence in situ hybridization (FISH) was used to examine CRART16 localization and expression. Bioinformatics analysis was performed to predict the potential mechanism of CRART16, which was further validated by a dual-luciferase reporter assay. Differences in measurement data were compared using Student’s t test, one-way ANOVA followed by Dunnett’s test and two-way ANOVA.

Results

The novel lncRNA CRART16 was upregulated in Caco-2 CR cells. CRART16 overexpression reversed the effects of cetuximab on cell viability and reduced cetuximab-induced apoptosis. Meanwhile, CRART16 overexpression led to increases in the proportion of CD44+/CD133+ cells. In addition, CRART16 acts as a competing endogenous RNA (ceRNA) for miR-371a-5p to regulate V-Erb-B2 Erythroblastic Leukemia Viral Oncogene Homolog 3 (ERBB3) expression. MiR-371a-5p mimics counteracted the cetuximab resistance induced by CRART16 overexpression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that after CRART16 was overexpressed, the resulting differentially expressed mRNAs were mainly enriched in the MAPK signaling pathway.

Conclusions

CRART16 overexpression may contribute to cetuximab resistance through the miR-371a-5p/ERBB3/MAPK pathway. Additionally, CRART16 contributes to the acquisition of stemness properties.
Wild edible plants and mushrooms of the Bamenda Highlands in Cameroon: ethnobotanical assessment and potentials for enhancing food security
Authors: Fongnzossie Evariste Fedoung , Nyangono Christine Fernande Biyegue , Biwole Achille Bernard , Ebai Patricia Nee Besong , Ndifongwa Nina Bisi , Motove Jannet , Dibong Siegfried Didier
Published: March 2020

Background

In seasons of food shortage, local communities across Africa use wild edible plants and mushrooms (WEPM) that contribute significantly to food security by supplementing households’ diets and providing alternative income. In the Bamenda Highlands of Cameroon, their biodiversity is believed to be rapidly declining as a result of land use change. Despite their potential beneficial values, there has been only limited research on this topic in this area. This study aims to document traditional knowledge related to the use of plants and mushrooms for food purpose by indigenous people of the Bamenda highland.

Method

Ethnobotanical surveys were conducted in 6 localities (Mbengwi, Bafut, Nkwen, Mankon, Bambili, and Widikum) of the Bamenda Highlands of Cameroon, and 121 individuals were interviewed on commonly gathered and eaten WEPMs and their perception on their availability. Respondents were permanent residents selected based on their willingness to participate in the study. Specimens of recorded plants were collected and processed for future identification at the National Herbarium of Cameroon. Their nutritional potentials are discussed based on available literature.

Results

A total of 47 species were recorded including leafy vegetable, spices, fruits, roots/tubers, and mushrooms. The top 5 most frequent areAmaranthussp. (6.6%),Termitomycesclypeatus(6.4%),Irvingia gabonensis(5.2%),Ricinodendron heudelotii(5.1%), andAframomumsp. (4.5%). Leafy vegetable and spices are the most diversified group with 13 species each. All recorded species are important from nutritional and pharmaceutical points. However, many of their values remain uninvestigated, while their natural populations are facing threats of degradation.

Conclusion

WEPMs have great potential to contribute to food and nutritional security in the study area. Sound nutrients and metabolites profiling of poorly known species can enhance their contribution in addressing food insecurity.
Knowledge translation strategies for dissemination with a focus on healthcare recipients: an overview of systematic reviews
Authors: Chapman Evelina , Haby Michelle M. , Toma Tereza Setsuko , de Bortoli Maritsa Carla , Illanes Eduardo , Oliveros Maria Jose , Barreto Jorge O. Maia
Published: March 2020

Background

While there is an ample literature on the evaluation of knowledge translation interventions aimed at healthcare providers, managers, and policy-makers, there has been less focus on patients and their informal caregivers. Further, no overview of the literature on dissemination strategies aimed at healthcare users and their caregivers has been conducted. The overview has two specific research questions: (1) to determine the most effective strategies that have been used to disseminate knowledge to healthcare recipients, and (2) to determine the barriers (and facilitators) to dissemination of knowledge to this group.

Methods

This overview used systematic review methods and was conducted according to a pre-defined protocol. A comprehensive search of ten databases and five websites was conducted. Both published and unpublished reviews in English, Spanish, or Portuguese were included. A methodological quality assessment was conducted; low-quality reviews were excluded. A narrative synthesis was undertaken, informed by a matrix of strategy by outcome measure. The Health System Evidence taxonomy for “consumer targeted strategies” was used to separate strategies into one of six categories.

Results

We identified 44 systematic reviews that describe the effective strategies to disseminate health knowledge to the public, patients, and caregivers. Some of these reviews also describe the most important barriers to the uptake of these effective strategies. When analyzing those strategies with the greatest potential to achieve behavioral changes, the majority of strategies with sufficient evidence of effectiveness were combined, frequent, and/or intense over time. Further, strategies focused on the patient, with tailored interventions, and those that seek to acquire skills and competencies were more effective in achieving these changes. In relation to barriers and facilitators, while the lack of health literacy or e-literacy could increase inequities, the benefits of social media were also emphasized, for example by widening access to health information for ethnic minorities and lower socioeconomic groups.

Conclusions

Those interventions that have been shown to be effective in improving knowledge uptake or health behaviors should be implemented in practice, programs, and policies—if not already implemented. When implementing strategies, decision-makers should consider the barriers and facilitators identified by this overview to ensure maximum effectiveness.

Protocol registration

PROSPERO: CRD42018093245.
Laboratory studies evaluating the efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) for the treatment and control of flea infestations on dogs
Authors: Kryda Kristina , Mahabir Sean P. , Carter Lori , Everett William R. , Young David R. , Meyer Leon , Thys Mirjan , Chapin Sara , Holzmer Susan J. , Becskei Csilla
Published: March 2020

Background

Five studies were conducted to evaluate a novel oral combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), for efficacy against induced flea infestations, speed of kill and effects on flea reproduction on dogs.

Methods

Based on pre-treatment flea counts, dogs were randomly allocated to treatment with a single, oral dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) on Day 0. All dogs were infested with approximately 100 unfed, adult fleas (C. felis or C. canis) prior to treatment and weekly for 5 weeks post-treatment. In Studies 1, 2 and 3, the number of viable fleas were comb-counted at 24 h after treatment and after each weekly infestation; Study 2 also included groups treated with tablets containing sarolaner-alone (1.2 mg/kg), moxidectin-alone (24 µg/kg) or pyrantel-alone (5 mg/kg). In Study 4, flea counts were conducted at 3, 4, 8 and 12 h after treatment and subsequent weekly infestations to establish speed of kill. In Study 5 (flea reproduction), dogs were housed in an enclosure designed to facilitate collection of flea eggs.

Results

Efficacy of Simparica Trio™ against C. felis was ≥ 99.7% and against C. canis was 100% at 24 h after treatment and after subsequent infestations for at least 35 days. Treatment with sarolaner-alone had similar efficacy to Simparica Trio™, while moxidectin-alone and pyrantel-alone were no different from placebo at most time points. In Study 4, significant flea killing started at 4 h after treatment; by 8 h after treatment, all treated dogs were free of fleas. Following weekly re-infestation, the combination product reduced fleas by ≥ 97.8% within 12 h for 28 days. Simparica Trio™ reduced flea egg-laying by 100% for 35 days. No treatment-related adverse reactions occurred in any study.

Conclusions

A single dose of Simparica Trio™ at the recommended minimum dose provided highly efficacious and rapid treatment within 4 h of existing flea infestations and persistent control of fleas on dogs for 5 weeks. The efficacy against fleas resulted in 100% prevention of flea reproduction for over a month following a single oral dose.
Efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of five common tick species infesting dogs in the USA
Authors: Kryda Kristina , Mahabir Sean P. , Chapin Sara , Holzmer Susan J. , Bowersock Laurel , Everett William R. , Riner John , Carter Lori , Young David
Published: March 2020

Background

The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus.

Methods

Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 (45–55) unfed adult ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs received either a single oral dose of Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or placebo. Tick counts were conducted at 48 h post-treatment and after each subsequent weekly re-infestation for A. maculatum, D. variabilis, I. scapularis and R. sanguineus studies and at 48 hours or at 72 h post-treatment and after weekly re-infestation in the first and second A. americanum studies, respectively.

Results

No treatment-related adverse reactions occurred in any study. In all studies, placebo-treated dogs maintained infestations throughout the entire study duration, and dogs treated with Simparica Trio™ had significantly lower (P ≤ 0.0010) mean live tick counts than placebo-treated dogs at all time-points. Against A. maculatum, D. variabilis, I. scapularis and R. sanguineus, a single oral dose of Simparica Trio™ evaluated at 48 h post-treatment provided ≥ 98.9% efficacy against existing infestations, and within 48 h of re-infestation efficacy was ≥ 90.4% through at least Day 28 (except for R. sanguineus on Day 14 in a single study with an efficacy of 89.7%). Against A. americanum, Simparica Trio™ provided ≥ 99.4% efficacy at ≤ 72 h after treatment of existing infestations and maintained ≥ 98.4% efficacy at ≤ 72 h after re-infestation through at least Day 35.

Conclusions

A single dose of Simparica Trio™ administered orally at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel provided treatment and control of the common tick species infesting dogs in the USA for at least one month.
Efficacy of a novel oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea and tick infestations on dogs presented as veterinary patients in Europe
Authors: Becskei Csilla , Fias Daphne , Mahabir Sean P. , Farkas Robert
Published: March 2020

Background

A novel chewable oral tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) has recently been developed to provide persistent protection against flea and tick infections for a month, treatment of hookworm and roundworm infections and prevention of heartworm and lungworm disease in dogs. Two field studies were conducted to evaluate the safety and efficacy of Simparica Trio™ against natural flea and tick infestations on dogs in Europe.

Methods

Dogs with natural flea or tick infestations were allocated randomly to treatment on Day 0 with either Simparica Trio™ tablets (flea study: n = 297; tick study: n = 189) to provide 1.2–2.4 mg/kg sarolaner, 24–48 µg/kg moxidectin and 5–10 mg/kg pyrantel (as pamoate salt) or with NexGard® Spectra (afoxolaner + milbemycin oxime) according to the label instructions (flea study: n = 164; tick study: n = 91). Efficacy was calculated based on the mean percent reduction in live parasite counts compared to the respective pre-treatment counts on Days 14 and 30 in the flea study and on Days 7, 14, 21 and 30 in the tick study. To count the fleas, the dog’s entire coat was systematically combed using an extra fine-tooth flea comb until all fleas were removed. For the tick counts, the dog’s entire coat was searched manually. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea allergic dogs in the flea study. Palatability was assessed in both studies.

Results

Simparica Trio™ was well tolerated in both studies. Efficacy against fleas was ≥ 97.9% in the Simparica Trio™ group and ≥ 96.1% in the NexGard® Spectra group. Efficacy against ticks was ≥ 94.8% in the Simparica Trio™ group and ≥ 94.4% in the NexGard® Spectra group. Clinical signs of flea allergy dermatitis improved following treatment with Simparica Trio™. Simparica Trio™ tablets were voluntarily and fully consumed on ≥ 78% of the 485 occasions they were offered.

Conclusions

A single oral dose of Simparica Trio™ was safe and highly efficacious against naturally occurring flea and tick infestations for 1 month on dogs. Clinical signs of FAD improved following treatment. Simparica Trio™ was voluntarily and readily consumed by most dogs.
Field efficacy and safety of a novel oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against naturally acquired gastrointestinal nematode infections in dogs presented as veterinary patients in Europe and the USA
Authors: Becskei Csilla , Kryda Kristina , Fias Daphne , Follis Stacey L. , Wozniakiewicz Magda , Mahabir Sean P. , Farkas Robert
Published: March 2020

Background

Gastrointestinal nematodes are parasites that commonly infect dogs, and infections can be subclinical or may cause considerable clinical disease. Some species are zoonotic and may also cause clinical disease in humans. Year-round treatment of dogs is recommended to eliminate existing infections, which also indirectly reduces the potential for subsequent human exposure to zoonotic species. Here we present two studies that evaluated the safety and efficacy of a novel chewable oral tablet containing sarolaner, moxidectin and pyrantel against gastrointestinal nematode infections in dogs presented as veterinary patients in Europe and the USA.

Methods

Dogs naturally infected with Toxocara canis, Toxascaris leonina, Ancylostoma caninum and/or Uncinaria stenocephala were enrolled in the European study, and dogs naturally infected with T. canis were enrolled in the USA study. The animals were treated once orally with Simparica Trio™ tablets to provide 1.2–2.4 mg/kg sarolaner, 24–48 µg/kg moxidectin and 5–10 mg/kg pyrantel (as pamoate salt) or with a commercially available product according to the label directions as positive control. Efficacy was based on the post-treatment reduction in geometric mean egg counts (per gram feces) 7 or 10 days after treatment compared to pre-treatment egg counts.

Results

Simparica Trio™ was well tolerated in both studies. In the European study, geometric mean egg counts for T. canis, T. leonina, A. caninum and U. stenocephala were reduced by ≥ 98.3% in the Simparica Trio™ group and by ≥ 97.4% in the afoxolaner + milbemycin oxime group. In the USA study, geometric mean egg counts for T. canis were reduced by 99.2% in the Simparica Trio™ group and by 98.6% in the ivermectin + pyrantel group. In the USA study, 48 and 10 dogs in the Simparica Trio™ and the ivermectin + pyrantel group, respectively, were co-infected with A. caninum and the reduction in the post-treatment mean fecal egg counts were 98.6% and 74.7%, respectively.

Conclusions

A single oral administration of Simparica Trio™ chewable tablets was well tolerated and was effective in the treatment of dogs with naturally occurring gastrointestinal nematode infections presented as veterinary patients in Europe and the USA.
Efficacy of orally administered combination of moxidectin, sarolaner and pyrantel (Simparica Trio™) for the prevention of experimental Angiostrongylus vasorum infection in dogs
Authors: Becskei Csilla , Thys Mirjan , Doherty Padraig , Mahabir Sean P.
Published: March 2020

Background

Infection with Angiostrongylus vasorum may cause severe clinical disease, even death in dogs, however, due to the often non-specific clinical signs, diagnosis is not always straightforward. Regular prophylactic treatment may offer a safe means to protect dogs against infection. The efficacy of a novel oral endectocide containing moxidectin, sarolaner and pyrantel was investigated for the prevention of angiostrongylosis in dogs in three placebo-controlled, randomized, masked studies. The initial study (Study 1) determined the efficacious dosage of moxidectin in the combination product by evaluating three different dose levels, and two follow-up studies (Studies 2 and 3) confirmed the efficacy of the selected moxidectin dose.

Methods

Animals were infected orally with 200 infective third-stage larvae (L3) of A. vasorum and were treated 28 days later with the combination product or with placebo. Timing of dosing relative to infection allowed for efficacy to be evaluated against the immature adult (L5) stage. Dogs in Study 1 received treatments with oral tablets to deliver 3, 12 or 24 µg/kg moxidectin in combination with 2 mg/kg sarolaner and 5.0 mg/kg pyrantel (as pamoate salt) or placebo. In Studies 2 and 3, Simparica Trio™ tablets were administered to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy of the combination product was calculated as the percent reduction in adult worm counts at necropsy relative to placebo.

Results

In Study 1, the 3, 12 and 24 µg/kg moxidectin dosage in the combination product provided 7.2%, 54.5% and 94.7% efficacy against the immature adult stages of A. vasorum, respectively. Studies 2 and 3 confirmed that the efficacy of 24 µg/kg moxidectin combined with 1.2 mg/kg sarolaner and 5 mg/kg pyrantel in Simparica Trio™ was ≥ 92.9%. All three studies established that a single oral administration of 24 µg/kg moxidectin in the combination product provided effective prophylactic treatment for angiostrongylosis, reduced L1 production and fecal excretion and minimized the tissue damage to the lungs.

Conclusions

A single oral treatment of dogs with Simparica Trio™ providing moxidectin at a minimum dose of 24 µg/kg was efficacious in the prevention of angiostrongylosis.
Efficacy of a novel chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against four common tick species infesting dogs in Europe
Authors: Becskei Csilla , Liebenberg Julian , Thys Mirjan , Mahabir Sean P.
Published: March 2020

Background

Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe.

Methods

Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation.

Results

There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days.

Conclusions

These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.
Efficacy of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced ascarid infections in dogs
Authors: Becskei Csilla , Kryda Kristina , Thys Mirjan , Holzmer Susan , Bowersock Laurel , Fernandes Tiago , Meyer Leon , Reinemeyer Craig , Mahabir Sean P.
Published: March 2020

Background

Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L5) and adult T. canis, and adult T. leonina infections in dogs.

Methods

Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7–10 days after treatment compared to placebo control.

Results

Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study.

Conclusions

These studies confirm the efficacy of a single dose of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.
Efficacy of Simparica Trio™, a novel chewable tablet containing sarolaner, moxidectin and pyrantel, against induced hookworm infections in dogs
Authors: Becskei Csilla , Thys Mirjan , Kryda Kristina , Meyer Leon , Martorell Susanna , Geurden Thomas , Dreesen Leentje , Fernandes Tiago , Mahabir Sean P.
Published: March 2020

Background

Ancylostomatids (‘hookworms’) are among the most important zoonotic nematode parasites infecting dogs worldwide.Ancylostoma caninumandUncinaria stenocephalaare two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adultA. caninum, and adultU. stenocephalainfections in dogs.

Methods

Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control.

Results

Based on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4larval stage ofA. caninum, ≥ 99.8% against immature adult (L5)A. caninum, and 100% against adultA. caninumand adultU. stenocephala.

Conclusions

These studies confirm the efficacy of a single oral dose of a novel, chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4larval and immature adult (L5)A. caninum, and adultA. caninumandU. stenocephalainfections in dogs.
Evaluation of the speed of kill of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of Ixodes scapularis on dogs
Authors: Holzmer Susan , Kryda Kristina , Mahabir Sean P. , Everett William
Published: March 2020

Background

The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs.

Methods

Dogs were allocated randomly based on host suitability tick counts to treatment with a single dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days −2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation.

Results

No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28.

Conclusions

A single dose of Simparica Trio™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month.
Simultaneous 166Ho/99mTc dual-isotope SPECT with Monte Carlo-based downscatter correction for automatic liver dosimetry in radioembolization
Authors: van Rooij R. , Braat A. J. A. T. , de Jong H. W. A. M. , Lam M. G. E. H.
Published: March 2020

Background

Intrahepatic dosimetry is paramount to optimize radioembolization treatment accuracy using radioactive holmium-166 microspheres (166Ho). This requires a practical protocol that combines quantitative imaging of microsphere distribution with automated and robust delineation of the volumes of interest. To this end, we propose a dual isotope single photon emission computed tomography (SPECT) protocol based on 166Ho therapeutic microspheres and technetium-99 m (99mTc) stannous phytate, which accumulates in healthy liver tissue. This protocol may allow accurate and automatic estimation of tumor-absorbed dose and healthy liver-absorbed dose. The current study focuses on a Monte Carlo-based reconstruction framework that inherently corrects for scatter crosstalk between the 166Ho and 99mTc imaging. To demonstrate the feasibility of the method, it is evaluated with realistic phantom experiments and patient data.

Methods

The Utrecht Monte Carlo System (UMCS) was extended to include detailed modeling of crosstalk interactions between 99mTc and 166Ho. First, 99mTc images were reconstructed including energy window-based corrections for 166Ho downscatter. Next, 99mTc downscatter in the 81-keV 166Ho window was Monte Carlo simulated to allow quantitative reconstruction of the 166Ho images. The accuracy of the 99mTc-downscatter modeling was evaluated by comparing measurements with simulations. In addition, the ratio between 99mTc and 166Ho yielding the best 166Ho dose estimates was established and the quantitative accuracy was reported.

Results

Given the same level of activity, 99mTc contributes twice as many counts to the 81-keV window than 166Ho, and four times as many counts to the 140-keV window, applying a 166Ho/99mTc ratio of 5:1 yielded a high accuracy in both 166Ho and 99mTc reconstruction. Phantom experiments revealed that the accuracy of quantitative 166Ho activity recovery was reduced by 10% due to the presence of 99mTc. Twenty iterations (8 subsets) of the SPECT/CT reconstructions were considered feasible for clinical practice. Applicability of the proposed protocol was shown in a proof-of-concept case.

Conclusion

A novel 166Ho/99mTc dual-isotope protocol for automatic dosimetry compensates accurately for downscatter and allows for the addition of 99mTc without compromising 166Ho SPECT image quality.
Integral Method for Flow Induced Transverse Vibrations Analysis of Flexible Pipes
Authors: ANGHEL Viorel , SOROHAN Stefan
Published: March 2020

This paper reviews some existing studies and numerical methods used for flow induced transverse vibrations analysis of flexible pipes. An integral method, based on the use of Green’s functions, already used for different straight beam dynamic analysis is adapted for the proposed subject. This approximate method leads to a matrix formulation and to an eigenvalue problem for free vibration analysis. The presented approach is able to estimate also the critical fluid velocities. Effects of boundary conditions and of elastic foundation characteristics, Coriolis terms and of other parameters on dynamic behavior of a pipe, can be included. Some numerical examples are also presented for comparisons with results obtained by FEM or with other data from literature. They show good agreement.
Effect of Hydraulic Diameter on Potential Core Decay of Supersonic Jets
Authors: MOHANTA Prasanta Kumar , SRIDHAR B. T. N.
Published: March 2020

Various studies dealing with decay characteristics of circular and noncircular supersonic jets were conducted by previous researchers. But in these studies due emphasis was not given to the hydraulic diameter (Dh), shape factor (ζ) & the nozzle lip parameters which have significant impact on the characteristics of noncircular supersonic jet. In this study, it has been shown that these parameters played a significant role on supersonic core decay characteristics [2, 3, 6] of the jet. The scope of this study included supersonic core length (Lc), decay pattern, due to noncircular shaped nozzle. In the literature, the supersonic jet characterization and the related experimental correlation are available for optimum expansion conditions whereas for other expansion (under and over) conditions the experimental correlation is barely available. While investigating experimentally, new empirical relations were obtained which were the improved forms of earlier correlations for supersonic core length [4]. For experiments, six different types of nozzles (circular, hexagon, square, triangular, elliptical and rectangular) with the same exit to throat area ratio, convergent length and divergent length were used. The results obtained from the experimentally developed correlations were coherent with numerical results, experimental data and flow visualization.
Notes Regarding the Dynamics of an Airplane subjected to Vertical Gusts
Authors: MORARU Laurentiu , STOIA-DJESKA Marius
Published: March 2020

The behavior of the aircraft within turbulent atmosphere is a key aspect of design. Many books and articles deal with this topic. The current paper presents studies related to predicting the responses of aircraft flying through vertical gusts. The equations describing the dynamics of the longitudinal channel of the airplane are written to include the effect of the vertical wind. The paper includes comparisons of results provided by non-linear and linearized equations of motion.
Aerodynamic assessment of axisymmetric launchers in the context of multidisciplinary optimisation
Authors: ONEL Alexandru-Iulian , CHELARU Teodor-Viorel
Published: March 2020

The paper presents a fast mathematical model that can be used to quickly assess the aerodynamic force coefficients of axisymmetric launchers as functions of Mach number and angle of attack. The tool developed based on the proposed mathematical model can be used separately or it can be integrated in a multidisciplinary optimisation algorithm for a preliminary small launcher design.
Design of High Pointing Accuracy NPSAT-1 Satellite Attitude Systems of Armature Controlled DC Motor with utilization for PD Controller
Authors: RAJA M. , PRAKASH O.
Published: March 2020

An Attitude control system plays the important role to maintain the satellite to desired attitude orientations. The intended application of NANO satellite in low earth orbits (LEO) helps find transient responses with and without controllers. LEO satellites typically orbit at an altitude ranging between160-2000 km. LEO satellites are widely used for remote sensing, navigation, and military surveillance applications. The Nano NPSAT-1 satellite attitude control systems (ACS) are described in this research work. The high pointing accuracy attitude estimation and feedback control systems are presented. The design specifications have been taken to meet the accuracy requirements (desired value ≤ 0.2 seconds) of Nano satellite attitude control. The feedback signal from on-board sensors compared with reference orbit trajectory and implementation of the Proportional Derivative (PD) controller is constructed. An algorithm of Nano satellite (NPSAT-1) attitude control is implemented using MATLAB Tools. In addition, the closed loop poles help find the gain of the system using Root Locus (RL) methods. The satellite control system is used to improve the transient response like overshoot and settling time of the system. Thus, the design of attitude control to improve the rise time, the settling time, the maximum overshoot, and no steady state error was carried out.
Tensile strength Characteristics on Dissimilar Metal Friction Welding of Ti-6Al-4V & SS304L
Authors: RAMESH KUMAR R. , BABU J. M.
Published: March 2020

In this research, the method of friction welding joints in Titanium and Stainless Steel with aluminium interlayer coating is created. The friction welding process is a solid-state joining process of dissimilar or similar materials. This friction welding process needs high rotational speed and high forging pressure. Titanium and stainless steel materials melting temperatures are around 1600OC. Welding process which needed high-pressure, temperature and good velocity regions. Titanium and stainless steels are coated 300OC ranges to applied aluminium spray coating method with constant pressure. The source of the aluminium coating is strong titanium and stainless steel adhesive strength. In this experimental project, four different trials of titanium and stainless steel joints have been performed at different speeds and constant forging pressures. Trial 4 connections of titanium and stainless steel made of 2100OC temperature and forging pressure of 60 MPa, friction time of 5 sec and friction pressure of 70 MPa. Friction welding experiments were completed with the help of friction time, forging pressure, rotational speed and friction pressure. Tensile load stress results are calculated by the UTM machine and evaluated the results of design experts with ANOVA table and RSM.
Drilling of Hybrid Aluminum Matrix Composites using Grey-Taguchi Method
Authors: SARALA RUBI C. , UDAYA PRAKASH J.
Published: March 2020

Drilling is a very important hole making process. It is very much useful for assembly of parts. Incorporation of hard ceramic particles into the matrix of metallic composites made them difficult to machine. So, it becomes inevitable to optimize the drilling parameters. The foremost objective of this research work is to fabricate Hybrid Aluminium Matrix Composites(AMCs) of LM6/B4C/Fly Ash with 3%, 6% & 9% by weight percentages of both reinforcements, equally using stir casting technique. The next objective is drilling of composites with feed, speed, drill and percentage of reinforcement as input process parameters at three levels each by Taguchi’s Design of Experiments approach. The final objective is to optimize the drilling process parameters for achieving low thrust force, low surface roughness and minimum burr height using the multi-objective Grey Relational Analysis. Results reveal that drill material plays a major role, being closely followed by feed and speed.
Delamination mechanisms in fiber-reinforced composites structures tested at different loadings
Authors: STEFAN Adriana , PELIN George , DRAGOMIRESCU Alina , PETRE Alexandra , ILINA Sorina
Published: March 2020

Composite materials are a special class which has some advantages like low weight, high strength and stiffness. For a composite system they are very suitable for aerospace, marine and auto applications due to the low density. Among all the synthetic fibers, carbon fibers are now considered the first material to be used for reinforcement due to their proper cost, as compared to aramid, and better mechanical and physical properties. This paper is an experimental work and presents the preliminary results regarding the evaluation of CFRP prepreg based on M18/1 carbon fiber prepreg developed by manual lay-up/autoclave curing. The obtained materials were tested at different mechanical loads and the failure mode was analyzed with the aim of evaluating their performances. The mechanism by which the fibers are delaminated in the composite system is assessed. To verify if the structure has defects that can interfere with the delamination process, ultrasonic nondestructive testing has been used. Also, for a better understanding of the delamination mechanism, the numerical simulation was used.
TWQH Attitude Control Experiments on Horizon Ground Simulator and Flight Test
Authors: STOIAN Stefan Eugen , ION-GUTA Dragos Daniel , NICHIFOR Sandra Elena , SPERLEA Florentin , IONITA Achim
Published: March 2020

This paper presents the results of two experiments on the Horizon ground simulator and outdoor flight test of TWQH hybrid UAV in presence of wind perturbation. The simulation results show the stability and error boundedness of the PID controller while the experimental inflight tests indicate the good performances of the proposed controller.
Finite Element Analysis of Existing and Modified Intramedullary Rod for Orthopedic Applications
Authors: UDAYA PRAKASH J. , JAYAVELU S. , RAJKUMAR C.
Published: March 2020

Finite Element Analysis (FEA) has been used in the field of biomedical engineering and especially in biomechanics, which helps to predict and validate feasible designs for complex cases. The role of biomechanics has grown steadily in the field of orthopedic surgery. For example, fixation was performed to stabilize a large femoral bone fragment. Femoral injury is analyzed in real time, and the experiment provides a three-dimensional visualization of finite elements designed to explain the mechanical properties of the femur. Modified trapezoidal nail shape is used in the modified intramedullary rod setup in order to obtain additional strength and stability. It also provides resistance to femoral head rotation. Potentially it improves patient mobility and recovery since the modified design is in par with the anatomy of the human femur bone.
Topical Issues in Aircraft Health Management with Applications to Jet Engines
Authors: BERBENTE Sorin , ANDREI Irina-Carmen , STROE Gabriela , COSTEA Mihaela-Luminita
Published: March 2020

Aircraft Health Management Technology for jet engines represents a very important problem, since it develops a large impact on reducing the engine life cycle costs, improving the fuel efficiency, increasing the engines durability and life cycle. This technology is high-end and, in order to enable an improved level of performance that far exceeds the current one, propulsion systems must comply with terms of reducing harmful emissions, maximizing fuel efficiency and minimizing noise, while improving system’s affordability and safety. Aircraft Health Management Technology includes multiple goals of aircraft propulsion control, diagnostics problems, prognostics realized, and their proper integration in control systems. Modern control for Aircraft Health Management Technology is based on improved control techniques and therefore provides improved aircraft propulsion system performances. The study presented in this paper approaches a new concept, of attractive interest currently, that is the intelligent control; in this context, the Health Management of jet engines is crucial, being focused on engine controllers which are designed to match certain operability and performance constraints. Automated Engine Health Management has the capacity to significantly reduce the maintenance effort and propulsion systems’ logistical footprint. In order to prioritize and resolve problems in the field of support engineering there are required more detailed data on equipment reliability and failures detection and management; the equipment design, operations and maintenance procedures and tooling are also very important.
Identification of the critical parts for a medium courier turboprop aircraft
Authors: VOICU Marius-Alexandru , FUIOREA Ion
Published: March 2020

Each time an aircraft system fails, a series of steps are required to repair or restore the aircraft to full operational status. The steps include failure detection, fault isolation, disassembly to gain access to the defective element, repair, and so on. The frequency of the maintenance becomes a significant parameter in determining system support requirements. The maintenance frequency for a particular item depends very much on the reliability of that item. In order to exemplify this idea the present paper contains a series of analyzes whose purpose is to identify the critical parts for a medium courier turboprop aircraft operated by the Romanian Air Force.
Guidelines for Aircraft Composite Panels
Authors: RUSU Bogdan , BLINDU Simona BLINDU , MICU Andra , SOARE Valentin
Published: March 2020

The objective of this paper is to give a general perspective and present some elementary steps for manufacturing aircraft sandwich panel composites. Composite materials have been widely used in high performance sectors of the aerospace and automotive industry, and there is considerable knowledge and confidence in their static, dynamic and crashworthiness properties. Sandwich composites are becoming more and more used in airframe structural design, mainly for their ability to substantially reduce weight while maintaining their high mechanical properties. The steps for manufacturing a sandwich composite that meets all the requirements for exploitation are very precise and rigorous, involving specific design requirements, specific materials selection and specific manufacturing conditions starting with the lay-up procedure and up to the curing process inside an autoclave. After the curing process, destructive and nondestructive tests and experiments are performed on the composite structures in order to validate the products. At the same time, this paper presents a short briefing about the implication of 3D printing technologies with high temperature resistance resins for sandwich cores used in aerospace applications.