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At the outset of a clinical relationship, boundaries are created in order to define the therapeutic relationship, outline the treatment process, and explain the limits of confidentiality. Although clients initially agree to these conditions, there are instances when clients violate these boundaries by engaging in stalking behaviors against their mental health providers. It is estimated that between 10-20% of mental health professionals will be stalked by a client over the course of their careers. Stalking is a crime that does not discriminate, and there is no correlation between its occurrence and a clinician's skill level or experience. Despite this real threat to clinician safety, there is a lack of awareness and training on this issue and a majority of clinicians report feeling unprepared to handle such behaviors.

Many studies and reports, both governmental and academic, plus legislation, have suggested and some mandated the establishment of threat assessment teams to protect campuses. These teams have proliferated across university, college and community college campuses nationally. Despite these efforts, targeted violence continues in our communities and on our campuses. The community in and around Salem, Oregon has instituted a community-based approach, the Willamette Valley Adult Threat Advisory Team, that is seen by many as the future of targeted mass violence prevention. We examine the advantages and benefits of incorporating a community-based approach to threat assessment. and explore the role higher education can play in those efforts.

As part of collecting information for the purpose of threat assessment and management regarding a person of concern within an institution of higher education, a threat assessment and management team or another institutional official may request that a campus counseling center conduct a risk assessment of dangerousness-to-others. This study measured counseling center clinicians' training and experience in conducting risk assessments of dangerousness-to-others. Survey data from mental health providers practicing in counseling centers within institutions of higher education revealed that these practitioners had significantly less training and experience in assessing dangerousness-to-others as compared to the training and experience they have in assessing dangerousness-to-self. This lack of training and experience brings into question the appropriateness of counseling center mental health providers conducting these assessments.

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Tumor-associated macrophages (TAMs) promote metastasis and tumor cell extravasation, survival, and growth. In hepatocellular carcinoma (HCC), the presence of TAM subpopulations correlates with poor outcome. In this issue of the JCI, Ning et al. report on their use of cell culture, mouse models, and human data sets to investigate the interactions between aerobic glycolysis and carbonic anhydrase XII (CA12) expression in HCC. Aerobic glycolysis promoted CA12 upregulation in TAMs, which induced a protumoral phenotype to promote tumor growth and metastasis. Tumor cell factors derived from HCC samples induced CA12 upregulation in tumor-infiltrating TAMs via the HIF1[alpha] pathway. In preclinical models of HCC, CA12 inhibition reduced tumor growth and lung metastasis and reduced TAM infiltrate. Notably, dual treatment with anti-PD1 and CA12 inhibitors synergistically attenuated tumor growth and metastasis and enhanced survival compared with either treatment alone. These findings suggest that targeting CA12 in combination with immune-checkpoint blockade may provide treatment options for HCC., Tumor-associated macrophages have protumoral functions Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the primary and metastatic tumor microenvironments (TMEs). In most cases in human cancers, their [...]

The earliest blood vessels in mammalian embryos are formed when endothelial cells differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium is thought to expand solely by proliferation of pre-existing endothelial cells. Here we show that a complementary source of endothelial cells is recruited into pre-existing vasculature after differentiation from the earliest precursors of erythrocytes, megakaryocytes and macrophages, the erythro-myeloid progenitors (EMPs) that are born in the yolk sac. A first wave of EMPs contributes endothelial cells to the yolk sac endothelium, and a second wave of EMPs colonizes the embryo and contributes endothelial cells to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognized source of endothelial cells, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing endothelial cells and the incorporation of endothelial cells derived from haematopoietic precursors.New blood vessel endothelial cells arise from differentiation of erythro-myeloid progenitor cells to complement the proliferation of pre-existing endothelial cells., Author(s): Alice Plein [sup.1] , Alessandro Fantin [sup.1] , Laura Denti [sup.1] , Jeffrey W. Pollard [sup.2] , Christiana Ruhrberg [sup.1] Author Affiliations:(1) UCL Institute of Ophthalmology, University College London, [...]

The authors respond to Goodwin's (2014) "Threat Assessment: Are We Using the Wrong Nets?" and use that article as a springboard to discuss various aspects of the threat assessment and management process. We find that Goodwin misses critical elements of the threat assessment and management process, conflates the process with two types of risk assessment, does illuminate some important concerns about the use of instrumentation, but incompletely addresses counseling center staff challenges in assisting the implementation of campus threat assessment and management teams.

In this issue of the JCI, Panigrahy et al. demonstrate that preoperative administration of the antiinflammatory drug ketorolac or specialized proresolving mediators (SPM) called resolvins increases disease-free survival rates and prevents metastasis after surgery and chemotherapy in mouse models of cancer. The antitumor response was partially mediated by tumor- specific T cell immunity and immunological memory., When treatment also promotes disease A century after Virchow hypothesized the association between inflammation and cancer, it is becoming evident that inflammatory mediators lead to cancer progression and metastasis (1). [...]

Although specialty board certification by the American Board of Professional Psychology (ABPP) has been a valued standard for decades, the vast majority of counseling psychologists do not pursue board certification in the specialty. The present article provides a brief history of board certification in general and some historical information about the history of board certification in counseling psychology specifically. In addition, information about the examination process and some of the advantages of board certification for individuals as well as for the field of counseling psychology are provided. It is the authors' hope that the information provided will invite counseling psychologists across settings to (re)consider becoming board certified. (Contains 1 note.)

This article provides an overview of threat assessment and management as implemented on campuses of higher education. Standards of practice and state calls for implementation are cited. An overview of some of the basic principles for threat assessment and management implementation is accompanied by examples of how they are utilized. Pitfalls inherent to threat assessment and management and suggested remedies are outlined. Finally, there is a brief introduction for the articles that follow in this special section.

Background and aims: Dickkopf‐1 (DKK1) is associated with poor prognosis in intrahepatic cholangiocarcinoma (iCCA), but the mechanisms behind this are unclear. Here, we show that DKK1 plays an immune regulatory role in vivo and inhibition reduces tumour growth. Methods: Various in vivo GEMM mouse models and patient samples were utilized to assess the effects of tumour specific DKK1 overexpression in iCCA. DKK1‐driven changes to the tumour immune microenvironment were characterized by immunostaining and gene expression analysis. DKK1 overexpressing and damage‐induced models of iCCA were used to demonstrate the therapeutic efficacy of DKK1 inhibition in these contexts using the anti‐DKK1 therapeutic, DKN‐01. Results: DKK1 overexpression in mouse models of iCCA drives an increase in chemokine and cytokine signalling, the recruitment of regulatory macrophages, and promotes the formation of a tolerogenic niche with higher numbers of regulatory T cells. We show a similar association of DKK1 with FOXP3 and regulatory T cells in patient tissue and gene expression data, demonstrating these effects are relevant to human iCCA. Finally, we demonstrate that inhibition of DKK1 with the monoclonal antibody mDKN‐01 is effective at reducing tumour burden in two distinct mouse models of the disease. Conclusion: DKK1 promotes tumour immune evasion in iCCA through the recruitment of immune suppressive macrophages. Targeting DKK1 with a neutralizing antibody is effective at reducing tumour growth in vivo. As such, DKK1 targeted and immune modulatory therapies may be an effective strategy in iCCA patients with high DKK1 tumour expression or tolerogenic immune phenotypes. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis is the main cause of death from breast cancer. In mouse models of breast cancer lung metastasis, macrophages enhance metastasis by promoting tumor cell seeding and persistent growth. Here, we show that interleukin-4 (IL4) is required for this process as IL4 receptor (IL4rα)-null mice develop fewer and smaller lung metastases. This deficiency is partially rescued by adoptive transfer of wild-type monocytes. IL4 signaling in macrophages upregulates the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. In addition, expression of several other genes already causally associated with lung metastasis including Ccl2, Csf1, Ccr1, Hgf and Flt1 are upregulated in macrophages. High-resolution intravital imaging at the time of metastatic seeding showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages, showing the dependence on IL4. We conclude that IL4 signaling in monocytes and macrophages is important during seeding and growth of breast metastasis in the lung. Metastasis is the systemic manifestation of cancer and the main cause of death from breast cancer. In mouse models of lung metastases, recruitment of classical monocytes from blood to the lung and their differentiation to metastasis-associated macrophages (MAMs) facilitate cancer cell extravasation, survival and growth. Ablation of MAMs or their monocytic progenitors inhibits metastasis. We hypothesized that factors controlling macrophage polarization modulate tumor cell extravasation in the lung. We evaluated whether signaling by Th1 or Th2 cytokines in macrophages affected transendothelial migration of tumor cells in vitro. Interferon gamma and LPS inhibited macrophage-dependent tumor cell extravasation while the Th2 cytokine interleukin-4 (IL4) enhanced this process. We demonstrated that IL4 receptor (IL4rα)-null mice developed fewer and smaller lung metastasis in E0771-LG mammary cancer models of this disease. Adoptive transfer of wild-type monocytes to IL4rα-deficient mice partially rescued this phenotype. IL4 signaling in macrophages controlled the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. Furthermore, IL4 signaling in macrophages regulated the transcript abundance of several other genes already causally associated with mammary cancer lung metastasis including Ccl2, Csf1, Ccr1, Hgf and Flt1. The central role of IL4 signaling in MAMs was confirmed by high-resolution intravital imaging of the lung in mice at the time of metastatic seeding, which showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages. This interaction with wild-type MAMs enhanced tumor cell survival and seeding, which was lost in the IL4rα mice. These data indicate that IL4 signaling in monocytes and macrophages is key during seeding and growth of breast metastasis in the lung, as it regulates pro-tumoral paracrine signaling between cancer cells and macrophages. [ABSTRACT FROM AUTHOR]

Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the 'hallmarks' of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases., Macrophages, which were originally identified by Metchnikoff on account of their phagocytic nature, are ancient cells in metazoan phylogeny. In adult mammals, they are found in all tissues where they [...]

Macrophages, which are abundant in the tumour microenvironment, enhance malignancy [1]. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells [2]. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis invivoand prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer [3-6]. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer., To understand the origin of macrophages in primary tumours and their metastatic sites, we measured monocyte trafficking. Mouse monocytes were identified by their expression of CD11b and CD115 (Supplementary Fig. [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.06.019 Byline: Shira Landskroner-Eiger (a), Jiyoung Park (b), Davelene Israel (c), Jeffrey W. Pollard (d), Philipp E. Scherer (b) Keywords: Mammary gland; Stroma; Adipocytes Abstract: Mammary gland development is critically dependent on the interactions between the stromal and the epithelial compartments within the gland. These events are under the control of a complex interplay of circulating and locally acting hormones and growth factors. To analyze the temporal and quantitative contributions of stromal adipocytes, we took advantage of the FAT-ATTAC mice (apoptosis through triggered activation of caspase-8), a model of inducible and reversible loss of adipocytes. This loss can be achieved through the induced dimerization of a caspase-8 fusion protein. In the context of female mice, we can achieve ablation of mammary adipocytes relatively selectively without affecting other fat pads. Under these conditions, we find that adipocytes are essential for the formation of the extended network of ducts in the mammary gland during puberty. Beyond their role in development, adipocytes are also essential to maintain the normal alveolar structures that develop during adulthood. Loss of adipose tissue initiated 2weeks after birth triggers fewer duct branching points and fewer terminal end buds (TEBs) and also triggers changes in proliferation and apoptosis in the epithelium associated with the TEBs. The reduced developmental pace that adipocyte-ablated glands undergo is reversible, as the emergence of new local adipocytes, upon cessation of treatment, enables the ductal epithelium to resume growth. Conversely, loss of local adipocytes initiated at 7weeks of age resulted in excessive lobulation, indicating that adipocytes are critically involved in maintaining proper architecture and functionality of the mammary epithelium. Collectively, using a unique model of inducible and reversible loss of adipocytes, our observations suggest that adipocytes are required for proper development during puberty and for the maintenance of the ductal architecture in the adult mammary gland. Author Affiliation: (a) Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA (b) Touchstone Diabetes Center, Departments of Internal Medicine & Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA (c) Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA (d) Departments of Developmental and Molecular Biology, Center of Reproductive Biology and Women's Health, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA Article History: Received 15 October 2009; Revised 10 June 2010; Accepted 11 June 2010

Successful embryo implantation requires complex interactions between the uterus and embryo, including the establishment of maternal immunologic tolerance of fetal material. The maternal-fetal interface is dynamically populated by a wide variety of innate immune cells; however, the relevance of uterine DCs (uDCs) within the decidua to the success of implantation has remained unclear. In this issue of the JCI, Plaks et al. show, in a transgenic mouse model, that uDCs are essential for pregnancy, as their ablation results in a failure of decidualization, impaired implantation, and embryonic resorption (see the related article beginning on page 3954). Depletion of uDCs altered decidual angiogenesis, suggesting that uDCs contribute to successful implantation via their effects on decidual tissue remodeling, including angiogenesis, and independent of their anticipated role in the establishment of maternal-fetal tolerance., Placental viviparity, a mode of reproduction during which nutrients are supplied to the embryo directly from the mother via the placenta, poses a number of challenges. The first is the [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.01.007 Byline: John Condeelis (1)(2), Jeffrey W. Pollard (3)(4) Abstract: Macrophages within the tumor microenvironment facilitate angiogenesis and extracellular-matrix breakdown and remodeling and promote tumor cell motility. Recent studies reveal that direct communication between macrophages and tumor cells leads to invasion and egress of tumor cells into the blood vessels (intravasation). Thus, macrophages are at the center of the invasion microenvironment and are an important drug target for cancer therapy. Author Affiliation: (1) Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA (2) Analytical Imaging Facility, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA (3) Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA (4) Department of Obstetrics & Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA