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Eric D Bateman,1 Christopher O’Brien,2 Paul Rugman,2 Sally Luke,2 Stefan Ivanov,2 Mohib Uddin2,3 1Department of Medicine, University of Cape Town, Cape Town, 7700, South Africa; 2Research and Development, 3Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, SE-431 83, Sweden Objectives: To evaluate the efficacy and safety of AZD1981, a potent, specific antagonist of the CRTh2 receptor, as add-on therapy to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), in patients with persistent asthma with an allergic component.Patients and methods: In this placebo-controlled, parallel-group Phase IIb study, patients with persistent atopic asthma on ICS and LABA were randomized to receive 12 weeks of treatment with placebo or AZD1981 (80 mg daily, 200 mg daily, and 10 mg, 40 mg, 100 mg, or 400 mg twice daily [BID]). The primary end point was the mean change from baseline in predose, prebronchodilator forced expiratory volume in 1 second (FEV1) averaged over weeks 2, 4, 8, and 12 in the AZD1981-treatment group vs the placebo group. Secondary end points included other measures of lung function, symptoms, and asthma control, as well as standard measures of safety.Results: In total, 1,140 patients (99.7%) received study treatment. There were improvements in the primary end point across all treatment groups over 12 weeks of treatment. However, the improvement for the highest AZD1981 dose (400 mg BID) vs placebo was not statistically significant (0.02 L, P=0.58), preventing interpretation of statistical testing for the lower doses. AZD1981 was well tolerated, and the incidence of adverse events was comparable across placebo and treatment groups.Conclusion: In patients with allergic asthma receiving ICS and LABA therapy, the addition of AZD1981 at doses up to 400 mg BID failed to produce a clinically relevant improvement in lung function or any other measured end point, but appeared to have an acceptable safety profile. This clinical study is registered with ClinicalTrials.gov (NCT01197794). Keywords: allergic asthma, AZD1981, CRTh2 antagonist, efficacy, safety, eosinophils

We advance three propositions in this paper. First, teaching international business (IB) at any level needs to be theoretically driven, using mainstream frameworks to organize thinking. Second, these frameworks need to be made relevant to the experiences of the students; for example, by using them in case studies. Third, these parameters of rigor and relevance need to be seamlessly integrated. We then demonstrate these principles using Rugman's CSA-FSA matrix, describing both the theoretical and practical value of the framework. (Contains 1 figure.)

New country and host records of Trichogramma species for Turkey are presented. Trichogramma aurosum Sugonjaev & Sorokina is recorded for the first time from Turkey, and a new species, T. zerynthiae Polaszek & Bolu, is described. Morphological identification based on dissected male genitalia is supplemented by molecular sequence data. [ABSTRACT FROM AUTHOR]

Many studies have highlighted how numerous bacteria provide their hosts essential nutrients or protection against pathogens, parasites and predators. Nevertheless, the role of symbiotic microorganisms in the interactions between social insects and their parasites is still poorly known. Microdon (Diptera, Syrphidae) is a peculiar fly genus whose larvae are able to successfully infiltrate ant colonies and feed upon the ant brood. Using high throughput 16S rRNA gene amplicon sequencing, we provide the first microbiome survey of Mi. myrmicae larvae and larvae and workers of its host, Myrmica scabrinodis , collected from two sites in England. We analyzed the microbiome of the external surface of the cuticle and the internal microbiome of the body separately. The results clearly show that the Mi. myrmicae microbiome significantly differs from that of its host, while no substantial dissimilarity was detected across the microbiome of ant workers and ant larvae. Microdon myrmicae microbiome varies across the two analyzed sites suggesting that bacteria communities of Mi. myrmicae are derived from the environment rather than by horizontal transmission between hosts and parasites. Families Streptococcaceae, Carnobacteriaceae and Rizhobiaceae are dominant in My. scabrinodis , and Spiroplasma is dominant in ant workers. Microbiome of Mi. myrmicae larvae is mainly characterized by the family Anaplasmataceae, with Wolbachia as predominant genus. Interestingly, we found Serratia within both Mi. myrmicae and Myrmica larvae. Bacteria of this genus are known to produce a family of pyrazines commonly involved in ant communication, which could play a role in Microdon /ant interaction. [ABSTRACT FROM AUTHOR]

[Display omitted] (From left to right) Gonatocerus cincticipitis female; Gonatocerus cincticipitis male; and map of collecting sites in Japan. Photographs by Serguei V. Triapitsyn; map by H. Kusuhara. • • Gonatocerus cincticipitis is an egg parasitoid of green rice leafhopper, Nephotettix cincticeps. • •The previously reported genetic identity of Gonatocerus cincticipitis was incorrect. • • Gonatocerus cincticipitis is a member of a morphologically difficult species complex. • •Revised molecular identity of Gonatocerus cincticipitis facilitates its positive identification. Gonatocerus cincticipitis Sahad (Hymenoptera: Mymaridae) is an egg parasitoid of the rice pest, green rice leafhopper Nephotettix cincticeps (Uhler) (Hemiptera: Cicadellidae), in Japan and the Republic of Korea. Its molecular determination is reconsidered following the previous taxonomic misidentification, and its genetic separation from G. saipanensis (Doutt), a morphologically identical Gonatocerus sp. from Shimane Prefecture, Honshu Island in Japan, and other members of the Gonatocerus fuscicornis (Walker) species complex is demonstrated and discussed. DNA was successfully extracted from reared specimens of G. cincticipitis from Honshu and Kyushu islands in Japan, and the standard barcoding section of the mitochondrial cytochrome oxidase subunit 1 gene (COI) as well as two regions of nuclear ribosomal RNA, the D2 domain of 28S (28S-D2) and the internal transcribed spacer 2 (ITS2), were amplified and sequenced for genetic analyses. Both sexes of G. cincticipitis are redescribed and illustrated to facilitate their recognition. An updated morphological key to females of the Palaearctic species of Gonatocerus Nees ab Esenbeck is also provided. [ABSTRACT FROM AUTHOR]

The Euwallacea fornicatus species complex is native to Asia but has invaded many countries globally. This complex includes four cryptic species that infest a wide range of economic crops, including tea. One of them is Euwallacea perbrevis Schedl, which has been a major pest of tea in Sri Lanka and India for over a century. The species complex was first recorded infesting tea in Taiwan over 80 years ago but the specific identity of that first record is unknown. Furthermore, although tea is an important industry in Taiwan, this pest has attracted limited attention. Hence, we surveyed tea gardens across the island, determining infestation rates, and identifying the Euwallacea species present. We also used sticky traps to monitor the annual flight dynamics of the beetles and of a parasitoid natural enemy, an undescribed species of Eucosmophorus. Levels of infestation varied even between neighboring gardens. Highly infested tea gardens were located mainly in central Taiwan and some in eastern Taiwan. The peak flight activity of the species complex occurred between October and March, when the parasitoid was also abundant. Molecular identification of the trapped beetles identified them as E. fornicatus sensu stricto Eichhoff and E. kuroshio Gomez & Hulcr, but E. perbrevis was not detected. In contrast to the situation in Sri Lanka, where E. perbrevis attacks the highly visible terminal branches of the tea plant, in Taiwan, E. fornicatus s. s. and E. kuroshio predominantly attacked the main bole and underground parts. We propose that the 'hidden' nature of this attack, and the similarities of the symptoms to a common fungal disease of tea, may have led to an underestimation of the impact of the species complex on tea, not only in Taiwan but also in other tea growing countries. • E. fornicatus s. s. and E. kuroshio are dominant in tea gardens of Taiwan. • E. perbrevis was not detected in tea gardens of Taiwan. • Peak flight activity of SHB occurred between October and March. • SHB prefer to attack lower part of the main trunk of the tea plant. [ABSTRACT FROM AUTHOR]

(From left to right) Amrasca biguttula adult and nymph; Anagrus ? atomus female; and A. turpanicus female. Photo by Tetsuya Adachi-Hagimori and Serguei V. Triapitsyn. [Display omitted] • Amrasca biguttula is an economically important pest of okra, Abelmoschus esculentus , in Japan. • Five species of Mymaridae and one of Trichogrammatidae were reared from okra leafhopper eggs. • Anagrus turpanicus was newly recorded from Japan. • Anagrus ? atomus , A. turpanicus and Pseudoligosita nephotetticum are for the first time reported from eggs of okra leafhopper. The okra leafhopper, Amrasca (Sundapteryx) biguttula (Ishida) (Hemiptera: Cicadellidae), is an economically important pest of okra, Abelmoschus esculentus (L.) Moench (Malvaceae), in Japan. During 2019 and 2022 surveys for its egg parasitoids (Hymenoptera) were conducted on Kyushu and Ryukyu islands in southern Japan. Five species of Mymaridae, Anagrus (Anagrus)? atomus (L.), A. (A.) japonicus Sahad, A. (A.) turpanicus Triapitsyn and Hu, Arescon enocki (Subba Rao and Kaur), and Stethynium empoascae Subba Rao, as well as one of Trichogrammatidae, Pseudoligosita nephotetticum (Mani), were recorded from eggs of A. biguttula on okra in Japan. Of these, A. (A.) turpanicus , identified using a combination of molecular and morphological methods, is newly recorded from Japan; A. (A.)? atomus , A. (A.) turpanicus and P. nephotetticum are for the first time reported from eggs of okra leafhopper. [ABSTRACT FROM AUTHOR]

Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology.Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated.Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively.Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. Objective We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. Methods Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. Results The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes. Conclusions A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters. [ABSTRACT FROM AUTHOR]