However, herein low CTX did not alter hemocytic cAMP even though

However, herein low CTX did not alter hemocytic cAMP even though hemocyte–glass and bacteria removal from the hemolymph was diminished and microaggregation enhanced. The effects of the holotoxin and its subunits on G. mellonella hemocytes appear to be cAMP-independent since levels of intracellular cAMP remain constant despite increasing physiological concentrations and increased only at a pharmacological level of CTX but not for CTB and decreased with CTA. In terms of vertebrate immunocytes, selleck screening library CTX cAMP-independent effects

are known to inhibit proliferation of B cells [31] and transmembrane signaling of Ca2+-stimulation of rat lymphocytes [25] and Jurkat cells [36]. CTB boosts innate immunity of murine B cells and macrophages

by cAMP-independent mechanisms increasing the phosphorylation of MEK1/2, ERH1/2 and p38 [63]. The mode of action of CTB on hemocytes is not clear, however, the effects of CTX on Swiss 3T3 fibroblasts are attributed to CTB binding to GM1 gangliosides elevating intracellular Ca2+ without modifying protein kinase C or phosphoinositides [13] and [67], the Ca2+ entering through L-channel modification by GM1 gangliosides as occurs in neuroblastoma cells [15]. Extracellular Ca2+ entering G. mellonella hemocytes check details via L-like channels stimulates hemocyte–glass adhesion [82]. Plasmatocyte phagocytosis of yeasts [6] and adhesion is enhanced by extracellular Ca2+ influx [82] but individual granular cell adhesion to slides is not [71]. However, both studies did not assess microaggregation. Extracellular Ca2+ cAMP is relevant to granular cell microaggregation with subsequent migration of plasmatocytes since calcium chelators and Ca2+-free buffers prevent hemocytic aggregations and granular cell cytoplasmic discharge [6]. CTX and CTB do not stimulate intracellular release of Ca2+ from the endoplasmic reticulum of vertebrate immunocytes [25] but chemically-generated intracellular Ca2+ release favours individual hemocyte adhesion [82].

Thus CTX and CTB may limit individual hemocyte types or subtypes adhering to glass by increasing cation influx while stimulating granular cell microaggregation. Alternatively Ca2+-influx might enhance microaggregation only making fewer cells available for adhesion to glass. CTB activates tyrosine kinases of macrophages eliciting TNF-α release [26] but inactive protein tyrosine kinases are required for G. mellonella hemocyte adhesive activities [82]. The results likely reflect differences in cell types since CTB differently affects endotoxin-stimulated macrophages and monocytes [63]. Results may be attributed also to the different types of enzyme inhibitors used altering different isoforms of the enzymes producing different effects. G.

Charts were reviewed for demographics, laboratory and imaging fin

Charts were reviewed for demographics, laboratory and imaging findings, and clinical course. 195 patients with suspected “eosinophilic pneumonia” demonstrated pulmonary eosinophilia (as defined above). Of these 195, 12 patients were included and 183 were excluded for various reasons (see Fig. 1). Thirteen patients were excluded due to relapse of symptoms on steroid

taper and 2 patients were Osimertinib ic50 excluded due to lack of diffuse infiltrates on chest imaging. Five patients had all characteristics consistent with the diagnosis of idiopathic AEP. Three patients were categorized as “probable” idiopathic AEP due to exceeding expected 30-day symptom duration (37 and 38 days) and/or maximal temperature less than 38 ○C and are included in analysis. Four patients were defined as “possible”

idiopathic AEP given history of polymyalgia rheumatica, eczema or allergic rhinitis and are described but not included in analysis. Clinical features of included patients are summarized in Table 1 and Table 2. While ZD6474 idiopathic AEP is by definition an acute illness, the symptom duration has been variably defined as less than 7 [11] or less than 30 days [2] without significant differences in the clinical manifestations. We examined all cases of possible idiopathic AEP of less than 45 days duration and describe two cases with symptoms slightly longer than 30 days as “probable” AEP. Although it can be argued that a longer duration of symptoms may lead to confusion with chronic eosinophilic pneumonia, the average duration of symptoms in chronic eosinophilic pneumonia is significantly longer (19.7 weeks) and the disease characteristics are distinct [13]. Likewise the definition of “febrile illness” varies in the reported literature including temperatures as low as 37.2 °C [6] and [12]. We used subjective fevers or a temperature of 38 °C. We have included one patient 3-mercaptopyruvate sulfurtransferase without fever who was using anti-pyretic agents. Little attention

has been made to the presence or absence of anti-pyretic agents or cooling device use in prior reported cases. Furthermore, patients with sepsis may have an abnormally low temperature in lieu of fever. It is unknown if this is also true of AEP as such patients have by definition been excluded from AEP criteria. With this in mind clinicians should consider AEP in patients in the absence of fever if other features are compatible. Hypoxemia has been typically described as a PaO2 less than 60 mm Hg or a pulse oximetry saturation of less than 90% on room air [2]. However, one recent case series did not use hypoxia/hypoxemia as an inclusion criteria for potential cases of idiopathic AEP [12]. In reviewing the literature, little attention has been paid to desaturation with activity. Some of our patients did not have hypoxia at rest but had hypoxia with minimal exertion. Desaturation with activity should be considered as a criterion for AEP. In patients without hypoxia but with other classic features AEP should be considered.

Pulmonary signs did not improve on treatment with antifungal A n

Pulmonary signs did not improve on treatment with antifungal. A new chest-CT scan revealed increased alveolar infiltrates in the right upper lung with bilateral pleural effusion. A thoracocentesis was PLX4720 performed, consistent with a transudate. A second videobronchoscopy with BAL and transbronchial biopsies were performed. Cytological

study revealed a total cell count of 3.600 cell/ml, 72% neutrophils, 20% macrophages and 8% lymphocytes, new cultures were negative. Histopathological examination of the lung biopsy revealed extensive neutrophils infiltration with fibrin at the alveolar level, edema and focal acute and organizing pneumonia. (Fig. 3). This histological findings were similar to the one performed in the skin.

Antifungal therapy was stopped. The patient was treated with methylprednisolone (500 mg IV for 3 days) followed by oral prednisone. Steroid therapy produced a rapid improvement of cutaneous and pulmonary involvement. Patient had rapid clinical and radiographic resolution. After 2 weeks of therapy, erythematous plaques and skin lesions decreased. No recurrence was observed and chest CT scan showed a substantial improvement. The SS was described by Robert Douglas Sweet in 1964, typical manifestations are cutaneous lesion and clinical symptoms improve after treatment with systemic steroids. Extra cutaneous symptoms associated with SS are commons, occurs in ±40% of clinical presentations. selleck compound Fever, arthritis, musculoskeletal and ocular involvements such as conjunctivitis,

uveitis, episcleritis have been reported frequently in literature.1 and 2 Pulmonary involvement is very rare, in our review of 34 cases, the ratio man: female was 1:1, the age average is 57 years – old (±14 years old, range 25–82 years old). In 18 cases hematological disorders such as myelodisplastic syndrome, myeloproliferative disorder, agnogenic myeloid metaplasia, refractory anemia with excess blasts and idiopathic thrombocytopenia Progesterone were present. Eight cases of SS with pulmonary involvement were in previously healthy people.9, 10, 12, 14, 16, 17, 23 and 27 Summary of demographic, clinical, diagnosis, treatment and outcome of cases reported in literature are shown in Table 1.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30 Skin involvement was the first manifestation in 16 of 34 cases. Typical symptoms are erythematous plaques and nodules, which may be recurrent and painful. Typical skin biopsy showed a dense infiltrate of neutrophils, primarily in dermis, associated to edema without vasculitis. In 12 of 34 cases, skins lesions and pulmonary involvements are simultaneous. If there is pulmonary involvement, it usually manifests with dry cough and dyspnea.11 Chest X-ray may reveal diffuse pulmonary infiltrated or pleural effusion, chest-CT usually confirms pulmonary involvement. Videobronchoscopy usually is normal.

Small amounts of 2-O-linked Araf units were also present The 13C

Small amounts of 2-O-linked Araf units were also present. The 13C NMR spectrum (Fig. 4C) of PF is in good agreement with the linkage analysis observed in the methylation analysis, with more intense anomeric signals of α-l-Araf units (at δ 107.3 and 108.3), β-Arap units (at δ 100.1) and β-d-Galp units (at δ 104.4) than that observed for

the galactoarabinoglucuronoxylan present in fraction STK-1000R. Finally, according to monosaccharide composition, methylation analysis and spectral data, fractions STK-1000R and PF contain galactoarabinoglucuronoxylans, with (1 → 4)-linked β-d-Xylp residues in the backbone, carrying branches exclusively in O-2. That present in STK-1000R is less branched, with side-chains formed by (1 → 5)-linked

α-l-Araf residues and (1 → 4)-linked α-d-GlcpA residues and with non-reducing end units formed DAPT order by α-l-Araf, β-Arap, β-d-Galp, α-d-GlcpA and 4-O-Me-α-d-GlcpA. Concerning fruits, acidic heteroxylans have been found only in monocotyledon pineapple (Smith & Harris, 1995), and in dicotyledons olive pulp (Vierhuis, Schols, Beldman, & Voragen, 2001), katamfe (Adesina & Higginbotham, 1977), winter melon (Mazumder, Lerouge, Loutelier-Bourhis, Driouich, & Ray, 2005) and in Siberian apricot (Odonmazig et al., 1990). With the exception of acidic heteroxylan from winter melon, where the branch point was unknown, the others were branched at O-2 and O-3. This is a usual pattern of branching in acidic heteroxylans that contain both Ara and GlcA units. In contrast, the acidic heteroxylans studied herein from the tamarillo pulp had a main chain branched only at O-2. The acidic heteroxylans from tamarillo pulp Angiogenesis inhibitor had a small amount of Galp found only as the non-reducing end in the methylation analysis. Due to the absence of other galactose derivatives in this analysis, which could possibly have arisen from a main chain of a contaminating pectic arabinogalactan, we believe that these Galp units belong to the acidic heteroxylan

structure. A detailed examination of the literature reveals that galactose occurs in the structural Janus kinase (JAK) features of some xylans isolated from various botanical sources. In these studies, galactose units were also found as non-reducing end-groups and were present in the pyranoside conformation ( Buchala, 1973, Buchala et al., 1972, Cipriani et al., 2008, Ebringerová et al., 1992, Shatalov et al., 1999 and Woolard et al., 1977). Regarding the biological properties of acidic heteroxylans, studies have already showed anti-ulcer (Cipriani et al., 2008), immunological (Ebringerová et al., 1998 and Proksch and Wagner, 1987), anti-complementary (Samuelsen et al., 1999) and antitussive activities (Kardosová, Maloviková, Pätoprstý, Nosál’ová, & Matáková, 2002). In this context and considering the use in folk medicine of tamarillo fruit, we also evaluated the antinociceptive and antiinflammatory effects of the galactoarabinoglucuronoxylan present in STK-1000R fraction.

, 2012c) It is clearly shown in Table 4 that the contents of dai

, 2012c). It is clearly shown in Table 4 that the contents of daidzein, genistein and glycitein increased after

2 h of hydrolysis for both experiments. Additionally, it has to be considered that there are other types of isoflavone glucosides in the soy molasses, which can also be converted to other forms at different proportions. VX-809 price The immobilised β-glucosidase presented minimal difference in conversion efficiency of isoflavones compared to the free enzyme, but this result may be explained by the lower enzyme accessibility to the substrate caused by the immobilisation process. This lower isoflavone hydrolysis efficiency exhibited by the immobilised enzyme can be compensated by reuse of the beads. The operational stability of immobilised cells containing β-glucosidase was evaluated at 50 °C using pNPβGlc or soy molasses isoflavones as substrates. In the first cycle the activity with pNPβGlc was 0.26 U/g; followed by 0.12 U/g and 0.04 U/g in the second and third cycles, respectively. The reaction product was not detected in the subsequent cycles. In the first cycle of isoflavone glucosides conversion, the rate of aglycones Alisertib supplier present in the total of isoflavones

was 11.3%, 23.7%, 39.1%, 72.7% and 95.3% with 0, 15, 30, 60 and 120 min of hydrolysis, respectively. There was no change in the concentration of aglycones during the second cycle of hydrolysis. These results indicate that the immobilisation system presents low stability at 50 °C. β-Glucosidase from Paecilomyces thermophila was capable of converting nearly all isoflavone glucosides (above 95%) and malonyl glucosides were little hydrolyzed by this enzyme in soybean flour extract ( Yang et al., 2009).

The results of isoflavone glucoside conversion in soy molasses by intracellular crotamiton β-glucosidase from D. hansenii UFV-1 are interesting because D. hansenii is a nonpathogenic yeast and it is found in various types of food. The use of immobilised yeast cells in calcium alginate by the food industry makes the enzyme more stable; thus the process is more economical and the conversion of isoflavone glycosides to their aglycone forms is possible, which means that the bioavailability of these compounds in soy molasses will be higher. Intracellular β-glucosidase from D. hansenii UFV-1 was produced, purified, characterised and also immobilised in calcium alginate. This enzyme presents promise for industrial applications since it showed great ability to hydrolyze isoflavone glucosides from soy molasses, in both its free and immobilised forms. The results reported indicate that the D. hansenii UFV-1 β-glicosidase may be used for establishment of a process to improve the nutritional value of soy products by hydrolyzing isoflavones in soy molasses to their aglycon forms.

Most bullae are poorly ventilated, and the amount of air trapped

Most bullae are poorly ventilated, and the amount of air trapped can be estimated through the difference in functional residual capacity by helium dilution and body plethysmography.7 The lung surrounding a bulla is less compliant, so that a bulla is preferentially

filled before the adjacent lung. The expansion of gas within a non-communicating bulla would exert a force which would account for the chest pain. The weakness in the arm we believe was likely to be neuropathic in origin. It could be explained through a direct pressure effect upon the brachial plexus. Theoretically, there could be serious consequences to an expanding pulmonary bulla, though empirical evidence is scarce: A young aeroplane passenger who unexpectedly died has been attributed to a lung bulla. The authors postulated that ABT-263 in vivo mTOR inhibitor mediastinal compression or a systemic air embolism could explain the sudden death.8 Pulmonary haemorrhage attributed to inflight pressure changes in a patient with emphysema and an enlarged bulla has been described.9 The support for our explanation of the symptoms is: 1) the recurrence of the symptoms, which

were predictable, always came on at altitude, and resolved whilst the plane descended and 2) the resolution of these symptoms with treatment of the bulla. No authors have any actual or potential conflict of interest including any financial, personal or other relationships that can influence or bias this case report. “
“Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is an increasingly popular investigation usually performed by chest physicians whereby enlarged mediastinal and hilar lymph nodes can be safely sampled under direct vision.1 It is usually performed under light sedation as a day Docetaxel cell line case procedure and takes approximately 20 min. EBUS-TBNA involves the use of a specialised ultrasound transducer integrated into a flexible fibreoptic bronchoscope which facilitates multiple biopsies to be taken under

direct vision. Doing so obviates many of the problems and issues associated with mediastinoscopy such as need for an inpatient stay, a neckline scar, risks of nosocomial infection and it has a smaller mortality rate. We present a case whereby recurrent breast cancer was diagnosed using this technique. A 67 years old female with a 40-pack-year smoking history presented with recurrent lower respiratory tract infections on a background of chronic obstructive pulmonary disease. Past medical history included left breast grade 2 invasive ductal carcinoma (T2 N1 (2 of 12) M0; ER8, PR6, Her-2 negative) eight years previously. Treatment consisted of chemotherapy prior to surgical excision, radiotherapy and Tamoxifen. Despite a normal chest X-ray, the history of recurrent infections led to a high resolution computed tomography scan to exclude structural lung disease. This showed subcarinal lymphadenopathy (Fig. 1), multiple nodules in the right lung and suggestion of lymphangitis.

Mink generally feeds on fish, birds, rodents and frogs (Gerell, 1

Mink generally feeds on fish, birds, rodents and frogs (Gerell, 1967). They are generalist predators and tend to feed on available prey (Clode and Macdonald, 2009) and the composition of the diet has been seen to differ between coastal and riverine mink (Ben-David et al., 1997) as well as between mink with habitats along rivers and mink with habitats

near lakes (Gerell, 1967 and Jedrzejewska et al., 2001). In our experience, coastal mink in Sweden has a higher frequency of fish in their stomach compared to inland mink (unpublished data). Age did not influence any of the concentrations of Trichostatin A solubility dmso PFAAs in the multiple regression models. The same was found in a study by Kannan et al. (2002b), where there were no age-related differences in PFOS concentrations between juvenile and adult mink. This underlines the possible difference in accumulation patterns in mink between PFAAs and lipophilic compounds such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as many C59 wnt molecular weight PCB

and PBDE congeners have been found to increase with age in wild male mink (Persson et al., 2013). In wild animals in general, there are contradictory reports of associations between PFAAs and age. For instance, there were indications of a lack of age related differences in PFOS concentrations in a study of adult and subadult Alaskan polar bears (Kannan et al., 2001), as well as in a study of ringed and gray seal in the Baltic sea (Kannan et al., 2002a). Regarding PFAAs with longer chain lengths, a study of Danish harbor seals

found no age relationship between age and concentrations of PFAAs with carbon chain length 6–11 (Dietz et al., 2012). In contrast, in a study on polar bears from East Greenland, age significantly influenced the summarized concentrations of perfluorinated acids (Sonne et al., 2008). In an earlier study on polar bears from the same area, concentrations of PFCAs with carbon chain length Methamphetamine 10–14 significantly increased up to six years of age in a subset of six polar bears, but there was no significant difference in concentrations between all adults and all subadults for any of the analyzed chemicals (Smithwick et al., 2005). In addition, there are reports of higher concentrations of some PFAAs in pups compared to adults in harbor seals (Ahrens et al., 2009 and Shaw et al., 2009), Baikal seals (Ishibashi et al., 2008) and Northern Sea otters (Hart et al., 2009), and it has been discussed that maternal transfer could be an important source of exposure. Notably, in an analysis of a subset of our data, concentrations of PFHxS and PFOS were significantly lower in 3–5 month old mink (n = 6, K area) than in the older mink (n = 20, K area, p < 0.01), but no significant differences were found for PFNA, PFDA or PFUnDA. This challenges the idea of a significant maternal transfer of PFAAs in mink.

Choice between the approaches may simply be a matter of preferenc

Choice between the approaches may simply be a matter of preference Protein Tyrosine Kinase inhibitor or convenience or data availability. Similarly, no important differences were found between spatial and non-spatial models (Biging and Dobbertin, 1995 and Windhager, 1999). Nevertheless, some notable

features emerged. Particularly good performance seems to coincide with strengths of certain models with respect to functional form or data used. For example, Moses, which uses open-grown tree relationships, performs particularly well for the prediction of open-grown trees. The strength of Prognaus is the prediction of poor sites, because it was fit from national inventory data. Silva and BWIN are considerably better in the prediction of pine than Moses and Prognaus, probably because pine is better represented in their datasets. We found that the expected general patterns of height:diameter ratio development are predicted well by all four individual-tree growth models. This indicates that

all four simulators were built using a general scientific concept that is logical and biologically reasonable. However, the results are highly variable, depending on the geographic region. There is excellent fit in some areas, whereas the fit in other areas is rather poor. It is interesting to note that areas of good fit seem to coincide for all four individual-tree growth models (e.g., Arnoldstein), this website even though they use a different model structure and were fit from different data. Probably frequently occurring growth patterns are well represented, whereas patterns of local importance are not so well described. Deviations in diameter increment models, height increment models, and crown ratio models are within a reasonable range for all four RAS p21 protein activator 1 simulators. Model performance depends strongly on the region where it is applied (compare Arnoldstein

vs. Litschau). Similarly, Schmid et al. (2006) found that efficiencies of the same model in different study areas can range from 0.583 (indicating very good model performance) to −0.911 (indicating bias). Coefficients of determination in their study between observed and predicted values ranged from 0.031 to 0.680, underlining highly variable performance. Height:diameter ratios can be a rather sensitive measure, because moderate deviations in either the height growth model or the diameter growth model can cause comparatively large discrepancies. Differences between observed and predicted height:diameter ratios can be as much as 13 units on average. This is large, given that differences between light and heavy thinning in growth and yield experiments can be as little as 1.8 at the beginning of the experiment and are as large as 25.3 units at the end (Röhle, 1995).

Many countries are likely to struggle to establish a well-functio

Many countries are likely to struggle to establish a well-functioning national ABS regulatory system. This will likely slow down and sometimes will block

the transfer of tree germplasm for R&D. Such a situation is unfortunate, as climate change, outbreaks of pests and diseases, and other ongoing productivity challenges, all increase the need for transferring tree germplasm to accelerate R&D. The continued need for germplasm transfers for research is well recognized by scientists and research institutes, who are pressing their BMN 673 governments to minimize the bureaucracy and costs related to the implementation of the Nagoya Protocol. Needs and options for specialized ABS arrangements for forest genetic resources to address concerns related to the Nagoya Protocol find more are also being explored by policymakers, in the context of FAO’s Commission on Genetic Resources for Food and Agriculture. We thank numerous colleagues who provided information for this report and apologize that the space does not allow them to be acknowledged individually here. We also thank two anonymous reviewers for their critical and thoughtful comments on an earlier version of this manuscript. “
“The development of biodiversity indicators to track the

rate of loss of biodiversity on a global scale has been underway for over two decades, first with the adoption of the Convention on Biological Diversity (CBD1) in 1992 (SCBD, 2001), followed in 2002 (SCBD, 2006) by the agreement on targets to reduce the loss of biological diversity by 2010 (the 2010 Biodiversity Target),

and most recently in 2010, by the adoption of the Aichi Targets and a revised and updated Strategic Plan for Biodiversity 2011–2020 (UNEP/CBD/COP, 2010). The rationale behind this work is a general recognition of the richness of biological diversity on Earth, the threats that human activities pose to this richness, and the negative consequences that further loss of diversity may have to mankind and to the before Earth biomes as a whole. The objectives of CBD refer to intrinsic and utilitarian values of biodiversity, including their importance for evolution and maintaining life-sustaining systems (Glowka et al., 1994). Its overarching goal of sustainable development is to ensure and enhance the livelihoods of millions of people under the challenge of balancing the human appropriation of nature with the effects of global climate change and a growing world population. According to CBD, biological diversity embraces the diversity of all life on Earth and is commonly distinguished at three levels: ecosystems, species, and genes. The values of biodiversity are generally associated with these levels.

Consistent with his Asperger’s disorder diagnosis, he had a diffi

Consistent with his Asperger’s disorder diagnosis, he had a difficult time with more abstract concepts, but excelled with the use of concrete, written materials. For example, the use of the social network circle allowed him to assess his support system in a visual way. The social nature of the group also provided important peer support and practice in sharing and engaging others. Youth 2 particularly benefited from the “Building Your Social Network” module. He initially endorsed having no friendships, but gradually added names of group members to his social network over the course of treatment. At the same time, NVP-BGJ398 concentration the difficulties inherent in having

an individual with an autism spectrum disorder in the group were apparent. As he became more comfortable in the group, he became very verbal and attention seeking with other members and was unable to recognize nonverbal social cues from group members and leaders. Toward the latter end of the group, his behavior required the group leaders to pull him aside often to explain why his behavior (e.g., butting in, taunting) was inappropriate (e.g., alienating others). At posttreatment, Youth 2 was still experiencing bullying on a daily basis, though he no longer reported any impairment from SAD. In regard to bullying,

he stated, “The group didn’t change [the bullying] Adriamycin but it helped a bit on how to handle it.” By the end of group, Youth 2 was regularly visiting his school counselor to discuss his victimization. He reported that bullying only mildly impacted his mood, relationships with friends and family, or school performance. Youth 3 was a 12-year-old, Caucasian seventh-grade boy who lived with his father and older sister. The boy’s mother passed away several years ago. His father (college graduate) worked in retail sales, earning an annual $30,000–40,000. At pretreatment, Youth 3 met criteria for SAD and GAD, with subclinical diagnoses of MDD and separation anxiety disorder (SEP). Youth 3 had few friends and reported a significant bullying history involving being teased, excluded from PtdIns(3,4)P2 groups, being called homophobic slurs, and being told that no one likes

him. He had also been punched by older kids in his neighborhood, excluded from lunch tables at school, and left out of games in the neighborhood. He reported that bullying most strongly impacted his relationship with his family as he became easily annoyed by his father and sister, didn’t want to spend time with them, and felt he couldn’t confide to his family. Youth 3 found the structure of the group helpful, enabling him to speak with peers about his problems. The structured role plays and exposure component also engaged his more creative side, and prompted him to think about solutions to bullying in ways that he had not before considered. For example, during the course of a role play about making new friends, he was especially persistent when trying to ask a confederate peer to “hang out.