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Prevention of infection with canine heartworm (Dirofilaria immitis) is based on the compliant administration of macrocyclic lactone (ML) drugs. Resistance to ML drugs is well documented in D. immitis; however, there remains a paucity of information on the spatial distribution and prevalence of resistant isolates. This project aims to improve understanding of ML-resistance by using a population genetic approach. We developed a large panel of microsatellite loci and identified 12 novel highly polymorphic markers. These 12, and five previously published markers were used to screen pools of microfilariae from 16 confirmed drug-susceptible, 25 confirmed drug-resistant, and from 10 suspected drug-resistant field isolates. In isolates where microfilarial suppression testing indicated resistance, Spatial Principal Component Analysis (sPCoA), Neighbor Joining Trees and Bayesian clustering all revealed high genetic similarity between pre- and post-treatment samples. Somewhat surprisingly, the Neighbor Joining tree and the sensitivity to detect a specific genetic signature for resistance. Future investigations using genomic analyses will be required to elucidate the genetic relationships of ML-resistant isolates.Background Although randomized controlled clinical trials are optimal to evaluate the effect of an experimental therapy, single-arm trials are required whenever randomization is unethical or not feasible, such as de-escalation studies. We propose using prospectively identified historical controls to place results of single-arm, de-escalation trials into context. Methods POSITIVE is a prospective, single-arm study in young women with hormone-receptor-positive early breast cancer to determine if temporarily interrupting adjuvant endocrine therapy in order to become pregnant increases the risk of a breast cancer event. After 272 women enrolled in POSITIVE, we identified a cohort of 1499 SOFT/TEXT patients potentially eligible to enroll in POSITIVE who did not interrupt endocrine therapy. Method I used the SOFT/TEXT cohort to calculate annualized hazard rates by a piecewise exponential model. Method II used the SOFT/TEXT cohort to group-match SOFT/TEXT patients to POSITIVE patients; sample sets of SOFT/TEXT patients were randomly drawn 5000 times to obtain sets having patient, disease, and treatment characteristics more balanced with POSITIVE participants. Results Compared with SOFT/TEXT, POSITIVE participants were younger, less likely to be overweight/obese, had fewer positive nodes, and fewer received aromatase inhibitor or chemotherapy. The estimated 3-year breast cancer free interval event rates were 9.5% (95% CI 7.9%,11.1%) for Method I and 9.4% (95% CI 7.8%,10.9%) for Method II, compared with 5.8% initially assumed when POSITIVE was designed. Conclusion External control datasets should be identified before launching single-arm, de-escalation trials and methods applied during their conduct to provide context for interim monitoring and interpretation of the final analysis.Gambling disorder and other comorbid addictive disorders may have similar underlying affective and motivational patterns. This study aims at examining the association between gambling disorder, comorbid addictive disorders (i.e., alcohol, drugs, spending, and videogames), positive and affective mood, and gambling motives in a community sample. A sample of 1099 adolescents and young adults was recruited from educational centres, from which 569 (51.7%) scored as non-problem gamblers, 42 (3.8%) as at-risk gamblers, and 53 (4.8%) as problem gamblers. Results suggest that enhancement, social, and coping motives are greater among problem gamblers and at-risk gamblers as compared to non-problem gamblers. Problem gamblers scored higher in gambling and comorbid disorders than at-risk gamblers, and also higher in gambling motives and negative mood when compared to non-problem gamblers. Likewise, gambling severity was significantly associated to gambling motives, negative mood, and other addictive disorders. read more Finally, enhancement motives were predictive of gambling, alcohol, drugs, and spending while controlling for the effect of age, sex, and positive and negative mood. These results shed light into the nature of the relationship between gambling and other comorbid addictions and can be used to tailor prevention and treatment strategies.The abilities to resolve flanker and Stroop interference, which are primarily mediated by the prefrontal cortex (PFC), have been shown to be dissociable at the individual difference level. However, the relationship between the neurocognitive development of these two aspects of interference control remains unclear. This study examined developmental changes in inhibition performance and PFC activation during flanker and Stroop interference control using functional near-infrared spectroscopy (fNIRS). Twenty-eight healthy children and adolescents aged 7-16 years (16 males) underwent the arrow flanker and color-word matching Stroop paradigms while changes in oxyhemoglobin concentration in the PFC were monitored by fNIRS. We found developmental improvements in inhibition performance in terms of the interference scores on both the flanker and Stroop tasks. There were also developmental increases in PFC activation, particularly in the medial region, while resolving flanker and Stroop interference. Despite developmental changes in inhibition performance and medial PFC activation during both tasks, the developmental changes that we observed for these two aspects of interference control were found to be relatively independent of each other. Our findings support the heterogeneous view of interference control and suggest that the neurocognitive development of flanker and Stroop interference control is only weakly associated, if not dissociable.Background Aderivative of Shiitake mushrooms, Lentinan is used to control malignant pleural effusion (MPE) through intrathoracic infusion. Purpose To determine the clinical response, survival and safety of Lentinan plus chemical irritants, and the optimal combinations with chemical irritants, indication, threshold and optimal regimen for achieving the desired responses. Study design We performed a new systematic review and meta-analysis following the PRISMA guidelines. Methods We collected all randomized controlled trials (RCTs) regarding Lentinan plus chemical irritants from Chinese and English electronic databases (from inception until March 2019). We evaluated their bias risk, synthesized data using meta-analysis, and summarized evidence quality following the Grades of Recommendation Assessment, Development and Evaluation approach. Results We included 65 RCTs involving 4,080 patients and nine chemical irritants. Most trials had unclear bias risk. Lentinan with cisplatin significantly improved complete response [Risk ratio (RR) = 1.