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Key Points Question Are incidence rates of US breast cancer molecular subtypes changing across age and racial/ethnic groups? Findings In this cross-sectional study including 320 124 women diagnosed with breast cancer from 2010 to 2016, incidence rates of luminal A breast cancer increased in non-Hispanic White and Asian/Pacific Islander women aged 40 to 69 years, and in non-Hispanic black women aged 55 to 69 years, for luminal B breast cancer in non-Hispanic White and Hispanic women of all ages, and for ERBB2-enriched breast cancer in non-Hispanic White women aged 25 to 39 years. Incidence rates for triple-negative breast cancer decreased in non-Hispanic Black and non-Hispanic White women aged 40 to 69 years. Meaning These findings of differing breast cancer molecular subtype–specific trends may suggest changes in the prevalence of breast cancer risk factors by race/ethnicity and age., This cross-sectional study examines the incidence of different molecular subtypes of breast cancers among different racial/ethnic and age groups., Importance Breast cancer incidence trends by age and race/ethnicity have been documented; it is less clear whether incidence trends of breast cancer molecular subtypes, which differ in risk factors and prognosis, also vary by age and race/ethnicity. Objective To estimate annual percentage changes and trends in breast cancer molecular subtype–specific incidence rates by age at diagnosis and race/ethnicity in the US. Design, Setting, and Participants This population-based cross-sectional study included data from 18 cancer registries in the Surveillance, Epidemiology and End Results database, capturing 27.8% of the US population. Hispanic and non-Hispanic White, Black, and Asian/Pacific Islander women aged 25 to 84 years who were diagnosed with invasive breast cancer from 2010 to 2016 were included. Data were analyzed from September 2019 to February 2020. Exposures Age and racial/ethnic groups. Main Outcomes and Measures Annual percentage change (APC) and 95% CIs for age-standardized breast cancer incidence rates stratified by 15-year age groups at diagnosis and race/ethnicity. Results Of 320 124 women diagnosed with breast cancer from 2010 to 2016, 232 558 (72.6%) had luminal A, 35 869 (11.2%) had luminal B, 15 472 (4.8%) had ERBB2-enriched, and 36 225 (11.3%) had triple-negative breast cancer subtypes. Luminal A breast cancer incidence rates increased in non-Hispanic White (APC from 2010-2014, 2.3%; 95% CI, 0.3% to 4.2%) and non-Hispanic Asian/Pacific Islander (APC from 2010-2016, 2.5%; 95% CI, 0.6% to 4.5%) women aged 40 to 54 years, and in non-Hispanic Black women aged 55 to 69 years women (APC from 2010-2012, 4.9%; 95% CI, 4.0% to 5.7%). Luminal B breast cancer incidence rates increased in all age groups for non-Hispanic White women (age 25-39 years: APC, 4.3%; 95% CI, 1.5% to 7.%2; age 40-54 years: APC, 3.5%; 95% CI, 1.4% to 5.6%; age 55-69 years: APC, 3.3%; 95% CI, 1.6% to 5.0%; age 70-84 years: APC, 3.9%; 95% CI, 1.9% to 6.0%) and Hispanic women (age 25-39 years: APC, 8.4%; 95% CI, 5.8% to 11.2%; age 40-54 years: APC, 6.1%; 95% CI, 4.2% to 8.0%; age 55-69 years: APC, 5.1%; 95% CI, 1.5% to 8.8%; age 70-84 years: APC, 7.1%; 95% CI, 4.6% to 9.6%) and in non-Hispanic Asian/Pacific Islander women aged 55 to 69 years (APC, 6.1%; 95% CI, 3.2% to 9.0%). ERBB2-enriched breast cancer incidence rates increased in non-Hispanic White women aged 25 to 39 years (APC, 4.7%; 95% CI, 1.5% to 8.0%). Triple-negative breast cancer incidence rates decreased in non-Hispanic White women aged 40 to 54 years (APC, –2.3%; 95% CI, –3.8% to –0.7%) and 55 to 69 years (APC, –3.6%; 95% CI, –5.1% to –2.1%) and in non-Hispanic Black women aged 55 to 69 years (APC, –1.4%; 95% CI, –2.2% to –0.7%). Conclusions and Relevance The findings of this cross-sectional study suggest that between 2010 and 2016, luminal A and luminal B breast cancer incidence rates increased for many racial/ethnic and age groups, with the largest increases observed for luminal B breast cancer. ERBB2-enriched breast cancer incidence rates increased for young non-Hispanic White women, while triple-negative breast cancer incidence rates decreased for midlife non-Hispanic White and non-Hispanic Black women. These trends may suggest changes in breast cancer risk factor profiles across age and racial/ethnic groups.

Oncolytic viruses (OVs) are the wild-type or genomic modified viruses, which can specifically replicate in cancer cells but not in normal cells. They cause cancer cell lysis and more importantly, their replication in tumor cells induces an antitumor immune response from the host. As synergistic stimulation of antitumor immune response requires multiple immune-regulatory factors, OVs armed with multiple immune-modulating factors are of high potential in cancer immunotherapy. We have constructed a novel herpes simplex virus type-1 virus (HSV-1), VG161, that is armed with IL12, IL15, and a unique PDL-1 peptide blocker. The aim of this study is to investigate the anticancer efficacy of VG161 in gastrointestinal (GI) cancers including gastric, hepatic, and colorectal cancers. The immune-stimulating activities in tumor-bearing immune competent mice were also demonstrated. VG161 was given to the tumor-bearing animals by intratumor injection (5 × 106-5 × 107 PFU/animal, once a day for 3-5 days). Antitumor activity of VG161 was tested in both immune-deficient mice as well as in immune-competent mice. Oncolytic activity of VG161 was demonstrated in human gastric (SGC-7901), hepatic (patient-derived xenograft, PDX), and colorectal (LS174T) cancer-bearing nude mice as the human tumors are susceptible to HSV infection and the immune system is compromised in those models. To determine the antitumor immune response activated by VG161, colorectal cancer (CT26) syngeneic model was used in immune competent animals and T cell subpopulation analysis, ELISPOT, and tumor rechallenge assay was applied to measure specific antitumor immunity. VG161 caused complete tumor eradication in PDX and CT26 tumor models and significantly inhibited tumor growth in SGC-7901 and LS174T models. All animals treated with VG161 survived for many months till sacrificed. In the CT26 model, no tumor could be found after rechallenging with the same tumor cells. The number of CD8+ tumor infiltrated T cells was significantly increased, and systemic specific anticancer immunity was confirmed by ELISPOT assay on T cells isolated from spleen. VG161 is a novel oncolytic virus that is both strong in oncolysis and stimulating antitumor immunity for GI cancers. Intratumorally expressing multiple immune-regulatory factors by an oncolytic virus may significantly change the GI tumor immune microenvironment and stimulate anticancer immunity, to further enhance the efficacy of the oncolytic virus. Citation Format: Ronghua Zhao, Jun Ding, Tianchi Liu, Shuyun Liu, Dmitry Chouljenko, Yanal Murad, Erica Lee, Guoyu Liu, Luke Bu, William Jia. Anticancer efficacy of a novel immune-stimulating oncolytic virus: VG161 in gastrointestinal cancers [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B85.

Prurigo pigmentosa is a rare inflammatory dermatitis first described in 1971. While the etiology of Prurigo pigmentosa is yet unknown, conditions associated with ketosis often accompany this rash. Prurigo pigmentosa is successfully treated with antibiotics and by resolution of ketosis. However, there is no dietary treatment option to successfully treat the rash without sacrificing ketosis. We report two cases successfully treated with increase of dietary carbohydrate intake. The second case suggests that cessation of ketosis may not be necessary to resolve Prurigo pigmentosa.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education series provides a comprehensive and contemporary review of basal cell carcinoma. The second article in this series will present both the current standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.

Research continues to elucidate the finding that children’s functioning is composed of numerous interdependent influences such as physical and psychological health, and ecological contexts which are inextricably linked. However, our nation’s healthcare delivery system has not traditionally followed this framework in adequately addressing whole-person needs within a holistic framework. This care has often been fragmented (i.e., physical health providers functioning separately from behavioral health providers) and not coordinated among the numerous systems (e.g., family, school, healthcare) in which children interact. This chapter aims to highlight the importance of using a broader systems orientation and social-ecological framework in pediatric healthcare delivery.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. The first article in this series describes our current understanding of this disease regarding epidemiology, cost, clinical and histopathologic presentations, carcinogenesis, natural history, and disease associations.

Resistance to the use of Indigenous themed mascots in North America has taken a variety of forms over the past several decades. This paper describes and analyses how a new vehicle for resistance, social media, can be integral to dismantling and eradicating racist images of Indigenous peoples. Specifically, this paper focusses on one campaign that questioned a high school sports mascot and team named the “Redmen”. By using examples from social media, the authors demonstrate how White settlers came to rely on the mascot imagery as a way to position themselves as superior and to regulate representations of Indigeneity. The authors’ analysis posits that the mascot is in itself a form of racialised colonial violence and they discuss how the name and mascot were protected by and through white settler surveillance and control. To intervene in this discourse of superiority and regulation, the paper describes how an anti-racist approach was used to design a social media campaign that built mass critical consciousness and a network of support within the community. The social media campaign coincided with and rallied support from the grassroots Indigenous Movement, Idle No More. The larger joint effort strategically and effectively redirected the public and critical focus to how the “Redmen” name and logo and other racist Indigenous mascots become normalised. Increased knowledge via social media catalysed a shift in public opinion which ultimately leads to retirement of the team name, logo and mascot.

This case describes a strategic planning process initiated by the division of student affairs at a small, private college. It presents several issues related to institutional identity, strategic planning initiative development, faculty and staff buy-in and stay-in, and the changing landscape of higher education. The case is designed for usage in educational leadership programs and is particularly pertinent to provoke discussions regarding leading from the middle, leadership for institutional change, and moral and ethical leadership. Students in educational leadership enrolled in student affairs leadership and administration courses, budgeting or strategic planning, or organizational theory courses can engage in discussion using multiple aspects of the case.

While science, technology, engineering and math hold the fastest growing fields today, only 44% and 36% of students are math and science ready, respectively, to enter college. By integrating the arts into STEM, a four-part origami based curriculum has been developed, which combines the topics of renewable energy, architecture design, 3D CAD design and printing, and mathematic, science, and engineering principles. The modules are composed of familiar engineering education tactics to get students to think outside of the box like an engineer. Students reverse engineer origami pieces, build an origami chair using the design process, and learn the topic of renewable energies through interactive games. The final module pulls the knowledge gained from the first three together. The students design and 3D print origami structures that are energy efficient and utilizes at least one source of renewable energy. Students go through the design process with brainstorming, prototyping, and working models. The K-12 Next Generation Science Standards for science and engineering has eight practices. Origami Meets STEAM practices all eight including: (1) Asking questions and defining problems, (2) Developing and using models, (3) Planning and carrying out investigations, and (6) Instructing explanations and designing solutions. This project has been introduced to 9th and 10th grade geometry classes. Surveys were given to gauge the effectiveness of activities with the students, teachers, and participating graduate students. This is a work in progress and results of the surveys and work are still being processed.

Oncolytic viruses (OVs) are among the most powerful approaches in cancer immunotherapy. OVs not only cause cancer cell lysis but more importantly, their infection in tumors induces anti-tumor immune response from the host, resulting in lasting anti-tumor immunity. It has been recognized that anti-tumor immune response requires multiple immune regulatory factors that act synergistically and tumor microenvironment is critical for tumor to grow. Herpes simplex virus type-1 (HSV-1) has been approved by FDA as an oncolytic viral drug to treat melanoma. One advantage of HSV-1 is its large genomic capacity for carrying multiple exogenous genes.A HSV-1 oncolytic viral vector (VG161) was constructed to simultaneously express IL12, IL15 with its receptor alpha unit and a PDL-1 blocking peptide. Antitumor activity of VG161 was tested in both immune competent mice (CT26 and A20 tumor models) and nude mice for human tumor models (LNCaP and U87). Since CT26 and A20 are poorly permissive for HSV-1 replication, the mouse tumor models were able to demonstrate the antitumor immune response induced by VG161 while oncolytic activity of VG161 was demonstrated in LNCaP and U87 models since the immune system is compromised in those models.VG161 completely inhibited tumors in all the models tested and the animals survived tumor-free for many months till sacrificed. VG161 induced tumor oncolysis in both LNCaP and U87 tumors. In the CT26 model, animals were protected from the second challenging with CT26 cells following previous virally induced tumor regression. Furthermore, in a A20 double tumor model, intratumoral injection into the tumor on one side caused tumor regression on both sides. Transcriptome analysis showed significant change in tumor microenvironment. Finally, tumor specific memory T-cells were evident in the treated animals. The anti-tumor immune response by VG161 was significantly stronger than similar viruses that did not express any immune stimulating gene or only express GM-CSF. These results showed that intratumorally expressed multiple immune regulatory factors by an oncolytic virus may significantly change the tumor immune microenvironment to enhance efficacy of the oncolytic virus. Citation Format: Ronghua Zhao, Jun Ding, Dmitry Choujenko, Yanal Murad, Erica Lee, Guoyu Liu, Luke Bu, William Jia. Synergistic activation of antitumor immunity by an oncolytic virus VG161 armed with multiple immune-stimulating genes [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B059.

Objective: Public, consumer and professional views about attention deficit hyperactivity disorder, its assessment and treatment – especially with medication – remain a highly contested domain. Parents in particular express disquiet with services. One response to this tension is a multidisciplinary evaluation. Parental and education perceptions of this process have not been evaluated previously. A community multidisciplinary approach was assessed in terms of diagnostic outcomes and client satisfaction. Method: A comprehensive multidisciplinary structured assessment of the first 50 referred children with severe attentional problems was documented. Demographic and symptom/behavioural profiles, developmental history and indicated multi-disciplinary evaluation were recorded. A team consensus process arrived at diagnostic classification. Post-assessment satisfaction of parents and school staff was surveyed. Results: Thirteen children (26%) were diagnosed with attention deficit hyperactivity disorder and three commenced stimulants. The majority of parents and educators were satisfied with the service. Conclusions: A multidisciplinary assessment clinic for children presenting with attention problems resulted in minimal prescribing. Overall, education staff and parents were satisfied with the service. The model may be a suitable response to the multiple concerns in the community.

This brief utilizes the most recent and rigorous financial aid research to inform state higher education leaders about innovative and effective financial aid practices. By simplifying aid eligibility requirements, improving the aid application process, and engaging in early awareness efforts, states could improve the effectiveness of existing aid programs. Additionally, by targeting aid in ways that encourage college completion, more students (particularly those who are most constrained by finances) will improve their chances of earning postsecondary degrees. In recent years, several states have adopted goals of greatly increasing educational attainment levels, so we argue that innovative financial aid policy reform is one of the necessary steps toward meeting these goals. This brief can inform ongoing policy negotiations between state commissioners of higher education, state education task forces, and education and workforce legislative committees. © 2013 Association for Education Finance and Policy

This study uses fixed-effects panel data techniques to estimate the elasticity of community college enrollment demand relative to local unemployment rates. The findings suggest that community college enrollment demand is counter-cyclical to changes in the labor market, as enrollments rise during periods of weak economic conditions. Using national data for the years 1990 through 2009, we find that a one percentage-point change in unemployment is associated with 1.1–3.3 % increases in enrollment demand. We disaggregate the analysis by total full-time and part-time enrollment, concluding that high levels of unemployment are also associated with greater demand for full-time attendance. Additionally, enrollments are slightly more responsive to unemployment in metropolitan (rather than micropolitan) areas. Informed by enrollment demand theory, our analysis provides an update to the “unemployment elasticity” literature and could aid in current enrollment planning, economic development, and public policy efforts to educate students on the margin between college and work.

Objectives Perinatal mortality prevention strategies that target fetal deaths often utilize vital records data sets shown to contain critical quality deficiencies. To understand the causes of deficient data, we linked survey responses of fetal death reporters with facility fetal death data quality indicators. Methods In 2011, we surveyed the person most responsible for fetal death reporting at New York City healthcare facilities on their attitudes, barriers, and practices regarding reporting. We compared responses by 2 facility data quality indicators (data completeness and ill-defined cause of fetal death) for third trimester fetal death registrations using Chi squared tests. Results Thirty-nine of 50 facilities completed full questionnaires (78 % response rate); responding facilities reported 84 % (n = 11,891) of all 2011 fetal deaths, including 329 third trimester fetal deaths. Facilities citing ≥1 reporting barrier were approximately five times more likely to have incomplete third trimester registrations than facilities citing no substantial barriers (37.5 vs 7.9 %; RR 4.7; 95 % CI [1.6–14.2]). Reported barriers included onerous reporting requirements (n = 10; 26 %) and competing physician priorities (n = 11; 28 %). Facilities citing difficulty involving physicians in reporting were more likely to report fetal deaths with nonspecific cause-of-death information (70.9 vs 56.6 %; RR 1.3; 95 % CI [1.1–1.5]). Conclusions Self-reported challenges correlate with completeness and accuracy of reported fetal death data, suggesting that such barriers are likely contributing to low quality data. We identified several improvement opportunities, including in-depth training and reducing the information collected, especially for early fetal deaths (

Oncolytic HSV-1 (oHSV-1) are among the most promising therapies for cancer. Besides the oncolytic activity delivered by the virus against tumor cells, this treatment can also induce a potent immune response against tumor antigens (whether classic TAA, or neoantigens specific to the tumor being targeted). We have constructed an oncolytic HSV-1 virus (VG161) to deliver 2 immunomodulator cytokines, IL12 and IL15, to the tumor micro-environment. These two cytokines can work synergistically to trigger an efficient anti-tumor immune response. A PD-L1 mimic peptide capable of blocking PD-1/PD-L1 interaction is also delivered as a Fc fusion peptide (TF-Fc) to help in maintaining an effective immune response against the tumor. For the construction of the recombinant virus, the exogenous components were cloned under CMV promoter control. The ICP34.5 gene was deleted as a safety measure for the recombinant virus. The expression of Il12, IL15 and TF-Fc were confirmed, in vitro and in vivo, by qRT-PCR, ELISA and Western blot. Upon intra-tumoral injection of VG161, expressed IL12, IL15 and TF-Fc were detected only in the injected tumor mass, but not in the animals' blood or other organs. The bio-distribution of the virus was tested by qPCR after injecting VG161 intratumorally, and most of the injected virus were concentrated in the tumor mass. Minimal amounts of the virus were detected in the liver and spleen for short periods after virus injection. We have demonstrated the superior activity of the VG161 virus, compared to the back-bone virus (with no payloads) using immune-competent mouse models (CT26) and nude mice implanted with human tumor cells lines (LNCaP and U87). VG161 induced tumor oncolysis resulting in complete tumor regression in nude mice. In the CT26 model, the tumor regressed to undetectable limits upon intra-tumoral injection with VG161. When the treated mice were challenged with the same tumor, the tumor cells did not grow. The added efficacy in CT26 tumor model can be attributed to the immune response generated by the modified virus, as demonstrated by a higher number of tumor-infiltrating CD8 T cells. The specific activity of T cells against the tumor cells was also demonstrated by ELISpot assay. Finally, memory T-cells were evident in the treated animals demonstrated by multiple assays. Conclusions This work has demonstrated the safety and efficacy of VG161, a novel oncolytic virus which can induce a strong anti-tumor immunity and oncolytic activity. We have also demonstrated that the Intra-tumoral expression of multiple immune regulatory factors may significantly change the tumor immune microenvironment to enhance the efficacy of the oncolytic virus. Citation Format: Yanal M. Murad, Jun Ding, Dmitry Chouljenko , Erica Lee, Luke Bu, Guoyu Liu, Ronghua Zhao, Zahid Delwar, Will Liu, William Jia. Synergy of immunomodulators delivered by an HSV-1 oncolytic virus can enhance its therapeutic effects in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5641.

Objective: This paper examines the concept of consumer participation in the context of developmental changes in parent/child relationships and associated differences in the utilization of child and adolescent mental health services. Method: Existing definitions and characteristics of mental health service delivery for children and young people are examined to answer the question ,“Who is the consumer in the context of clinical services for young clients and their parents, and does this change with the child or young person's developmental stage?”. Results: As children, young people and parents utilize services in this area of mental health, the roles of consumer and carer need redefinition to accommodate both young clients and parents as consumers, and parents also as carers. Conclusion: The proposed framework addresses the changing roles of parents and young clients from infancy to early adulthood to guide consumer and carer participation strategies. If child and adolescent mental health services are to apply a developmental perspective and engage both young clients and parents as ‘consumers’, they need to address challenges related to the differences in expectations and capacities of young clients and parents, to the complexity associated with dual roles, and to promoting meaningful participation.

Objective: To identify services supporting the well-being of infants and their families in an area of South Brisbane, Australia, highlight problems of accessing these services and recommend strategies to make them more readily available. Method: Semistructured interviews were conducted with staff from 18 service providers offering antenatal services, or programmes primarily focused on children under the age of 2 years and/or their families. The interview aimed to identify the precise nature of the services offered, problems encountered in providing those services, perceived gaps in services and potential strategies for improvement. Results: Services were diverse, provided by a range of different professionals, in varying locations (home, community, hospital) and with funding from various sources. The major findings were:(i) the fragmentation of services, lack of communication between them, and lack of continuity in services from one stage of family formation to another; (ii) the shortage of services working with the parents and infant together; and (iii) the difficulty ofproviding services for some at-risk populations. Conclusions: Recommendations included: (i) maintaining a range of different services networked through a centralized resource/referral centre; (ii) expandingjoint mother–infant services and providing training for such services; and (iii) supporting outreach services for difficult to engage populations.

Objective: To review the origins, processes, clientele and outcomes of a child and youth interagency forum, a collaborative response to children and youth with severe and complex presentations. Methods: After a description of the Forum origins, membership and processes, both qualitative and quantitative information is provided on the Forum clientele. The Forum's effectiveness is considered in terms of changes in services provided to this group, as well as changes in agency and interagency work practices. Results: Forum clients were predominantly boys aged 12 years, with an overrepresentation of indigenous and intellectually disabled children. Few lived with biological parents, and on average had experienced five schools, 11 or more residential placements and were involved with six agencies. Disruptive behaviour symptoms were common, as were suicidal thoughts or actions (43%), history of physical (50%) or sexual abuse (21%), alcohol (29%) and drug use (14%). On average Forum clients were taking three psychotropic medications. Forum client impairment ranged from major impairment to gross impairment across several domains. Conclusions: While this is not a formal outcome study, evidence suggesting Forum usefulness included qualitative feedback from agencies, altered clinical and interagency practices, and decreased client impairment. Practical interventions for clients with chronic, complex multidomain impairments are discussed in the context of current Australian child and adolescent mental health services.

Objectives: Our aim is to critique Australian child maltreatment policy, outline abuse trends and provide data on family risk factors. Method: We identified policy gaps and reviewed family profiles within selective child maltreatment databases. Data sources included international and Australian literature, Queensland Department of Child Safety reports and a research clinical database. Results: Data reviewed suggest that a pattern of co-occurring complex multiple system family problems characterize substantiated abuse cases. Conclusions: The presence of multiple family problems suggests the need for a new treatment paradigm. Multisystemic Therapy for child physical abuse and neglect is an evidence-based intervention that matches the therapeutic needs of such families.

Social Anxiety Disorder (SAD) is a potentially debilitating condition affecting approximately 12% of the population at some point in their life (Ruscio et al., 2008). SAD is divided into two subtypes: generalized and nongeneralized. Nongeneralized SAD refers to individuals whose fears are limited to one or two social situations, most commonly public speaking. Empirically supported treatments for public speaking anxiety generally include an exposure component (usually in vivo/simulated exposure). Exposure is often presented within the context of a habituation rationale, but cognitively- based therapies utilize a rationale for exposure based on cognitive restructuring and belief modification. Research investigating the incremental benefit of adding other treatment components to exposure has yielded mixed results; however, there is preliminary evidence that the context in which exposure is presented can have an impact on treatment outcome. Recently, acceptance-based therapies have begun to frame exposure as an opportunity to increase one's willingness to experience anxiety while engaging in valued behaviors, rather than as a vehicle for modifying maladaptive cognitions and reducing anxiety. However, little research has been conducted on the efficacy of acceptance-based therapies for public speaking anxiety, and no component control studies have examined the utility of an acceptance/cognitive defusion rationale and context for exposure. The present study compared exposure within an acceptance/defusion context to exposure with a habituation-based rationale in the treatment of public speaking anxiety. Treatment was delivered in a group format over 6 weekly sessions. The hypothesis of superior outcomes for the acceptance-based group was not supported by the data; no significant differences were found between the two treatment conditions. All participants improved on outcome measures of social/public speaking anxiety and speech quality (social skills).

The TAM family receptor tyrosine kinases, consisting of Tyro3, Axl and Mer, are implicated in a diverse range of cellular processes such as cell survival, proliferation, migration, angiogenesis, and inflammatory response. Despite the debates over their role as a driver in carcinogenesis owing to some recent findings, their link to human cancer is strongly supported by direct correlation of the level of expression/activity with tumor grade and prognosis. In particular, Axl was found to underlie metastasis as an essential regulator of the epithelial-mesenchymal transition (EMT) process and also to confer acquired resistance to the TKI-mediated targeted therapies by up-regulation of associated kinases. Currently, none of FDA-approved kinase drugs were developed for the TAM family kinases. In our effort to develop such small-molecule inhibitors targeting the TAM kinases for oncology indications, we uncovered a series of novel potent compounds with low nM potency against Axl and Tyro3. Effect of these compounds in human cancer cell lines of different tissue origins was mediated mainly through the Axl-dependent signaling pathways. Detailed analysis of signaling proteins downstream of Axl revealed different mechanisms of action for these compounds. In addition to suppression of cell proliferation, these compounds inhibited anchorage-independent colony formation, cell migration and invasion. Four compounds were selected to be evaluated in pharmacokinetic studies in mice and the results indicated that these compounds possess reasonable PK properties with high exposure, reasonably long half-life, and good bioavailability. The results of the efficacy studies in suppressing tumor growth in a xenograft and an orthotropic mouse models will be discussed. Citation Format: Hong Zhang, Zaihui Zhang, Xiaoqing Shi, Erica Lee, Rick Li, Yuxiang Hu, Jun Yan, Jasbinder Sanghera. Evaluation of compounds developed against the TAM family kinases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5393. doi:10.1158/1538-7445.AM2015-5393

This study was undertaken to determine whether overexpression of the oncogene HER-2 is associated with an increase in local recurrence in women with early stage breast cancer treated with breast-conserving therapy (BCT). A retrospective review of the medical records of all women treated with stage I-II invasive breast cancer from 1991 through 2001 was performed. Of 596 eligible patients treated in that time period, immunohistochemical testing for HER-2 expression was performed in 352 patients (59%): 266 patients (76%) were HER-2 negative and 86 patients (24%) were HER-2 positive. Median follow-up was 5.4 years. The patient characteristics for the two groups were compared for age, pathologic T and N stage, number of positive nodes, estrogen receptor (ER) and progesterone receptor (PR) status, radiation treatment, and use of hormonal therapy or chemotherapy. There were no significant differences in any of these parameters between the two groups (all p > or = 0.10). Local recurrence at 5 years was 2% in the HER-2-negative group and 0% in the HER-2-positive group (p = 0.15). There was no difference in local recurrence after BCT between HER-2-positive and negative breast cancers at 5 years. Therefore HER-2 overexpression does not appear to be a contraindication to BCT.

TAM family (Tyro3, Axl, and Mer) of receptor tyrosine kinases mediated signaling is involved in cell survival, proliferation, migration and adhesion, vascular smooth muscle homeostasis, platelet function and erythropoiesis, and regulation of inflammatory cytokine release. These RTKs are frequently co-expressed in vascular, reproductive, nervous, and immune system in adults. TAM family kinases can be activated by vitamin K-dependent ligands GAS6 and Protein S. Tyro3, Axl, and Mer also display ectopic or overexpression in numerous cancers, including myeloid and lymphoblastic leukemias, melanoma, breast, lung, colon, liver, gastric, kidney, ovarian, uterine, and brain cancers. Therefore, they represent another class of kinase targets for development of cancer therapy. In this study, we report the discovery of a new class of potent and selective inhibitors of TAM family. These new compounds have demonstrated in vitro potency in nM range against these kinases and selectivity against other kinases in a selected panel. Many of these new compounds can dramatically reduce the pAkt levels in several cancer cell lines in a dose dependent manner. In thymidine incorporation assay, some compounds showed inhibition of cell proliferation at sub-micromolar concentrations. Furthermore, some compounds have demonstrated efficacy in colony formation assays. The most promising compounds are now being selected for in vivo proof-of-concept studies. The pharmaceutical properties of these compounds together with ADME profile were also evaluated. Taken together, the data generated so far indicates that these new inhibitors of TAM family kinases represent a new approach for cancer therapy. Citation Format: Zaihui Zhang, Rick Li, Erica Lee, Yuxiang Hu, Jun Yan, Jasbinder Sanghera. Discovery of novel TAM family kinase inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2014-2716

Axl is a member of the TAM tyrosine kinase family and is activated by products of Gas6 and Protein S genes. Axl is overexpressed or overactive in breast, renal, endometrial, ovarian, thyroid, non-small cell lung carcinoma, uveal melanoma as well as in myeloid leukemias. It has also been demonstrated that Axl expression is upregulated in drug-resistant cancer cells. Knock-down of Axl by RNAi repressed tumor formation in MDA-231 breast carcinoma model. Downregulation of Axl expression by RNAi led to a decrease of K562/ADR and MCF-7/ADR cells invasion, proliferation, and increased cell chemosensitivity in vitro. In a xenograft model of MDR cells, downregulation of Axl enhanced the anticancer activity of chemotherapeutic drugs. Therefore, Axl is a potential target for the development of chemotherapeutic agents for cancer therapy. During our endeavor of discovering and developing Axl kinase inhibitors for cancer therapy, we have discovered a series of potent and selective Axl inhibitors. These new compounds have demonstrated nM potency against Axl and good selectivity against other kinases in a selected panel of kinases. Many of these new compounds can reduce the pAkt levels in several cancer cell lines in a dose dependent manner and demonstrated inhibition of cell proliferation at sub-micromolar concentration in thymidine incorporation assay. Several selected compounds have demonstrated efficacy in colony formation assays. The most promising compounds are now being selected for in vivo proof-of-concept studies. The pharmaceutical properties of these compounds together with ADME profile were also evaluated and will be reported. These new Axl inhibitors represent a new approach for cancer therapy. Citation Format: Zaihui Zhang, Rick Li, Erica Lee, Yuxiang Hu, Jun Yan, Jasbinder Sanghera. Novel and selective Axl inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1746. doi:10.1158/1538-7445.AM2014-1746

Commentary on: Sourander A, Multimaki P, Santalahti P, et al. Mental health service use among 18-year-old adolescent boys: a prospective 10-year follow-up study. J Am Acad Child Adolesc Psychiatry 2004; 43:1250–8. [Extract] Sourander et al replicate findings from other epidemiological studies that report mental health service utilisation by adolescent males is very low (approximately 2%). Further analysis identified a range of psychopathological symptoms (anxious–depressive and withdrawn symptoms) and other variables (health problems; not living with parents; illicit drug, alcohol, and cigarette use) that were independently associated with mental health service use in a multivariate model. These findings concur with identification of comorbidity and multidomain impairment in clinical child and adolescent mental health samples1 and highlight the need for an inclusive service response, such as the multisystemic therapy model,2 rather than fragmentation across different providers.

This study examines masculine imagery in the foreign affairs cartoons in Krokodil, a Soviet satirical magazine, from 1945 to 1955. Both the Soviet Union's leaders and its people faced two major issues in this time period: rebuilding the country after the devastation of the Second World War, and descending into the Cold War battle of ideology with the West. Enemy countries in the cartoons are almost always portrayed as male figures, and the cartoons manipulate the masculine images to denote power relationships between countries, and also between men. As in many countries that fought in the war, the Soviet Union prioritized rebuilding the family in postwar society. The catastrophic loss of life, particularly among the male population, made this task more difficult in the Soviet Union. The state therefore employed a variety of tactics to promote the family, and to ensure that men assumed their proper positions as husbands and fathers. Using Krokodil's cartoons to promote masculine identity among Soviet men - and demeaning it among enemy men - was one such method. The major argument of the paper is that the cartoons featuring enemy countries commented not only on those enemies, but on the domestic situation in the Soviet Union as well. Borrowing and building on the language of postcolonial theory, this paper argues that the Soviet Union defined itself against the characteristics it assigned to the enemy. The dichotomy of self and other in the cartoons extends past that of the Soviet Union and its national enemies, to the Soviet man and enemies to his masculinity. By portraying the country's enemies in various homoerotic situations in the cartoons, the Soviet Union sought to delegitimize the potency of the enemy, while also signaling to the Soviet population that the unmasculine behavior associated with the enemy in the cartoons would not be tolerated in the Soviet Union. Drawing on a wide range of literature, including studies of humor and satire, art and visual iconography, gender, masculinity, and queer theory, this paper uses the medium of political cartoons to link issues of sexuality with postwar reconstruction and Cold War animosity in the Soviet Union between 1945 and 1955.