Artificial APCs (aAPCs) genetically modified to express selective costimulatory molecules provide a reproducible, cost-effective, and convenient method for polyclonal and Ag-specific expansion of human T cells for adoptive immunotherapy. Among the variety of aAPCs that have been studied, acellular beads expressing anti-CD3/anti-CD28 efficiently expand CD4+ cells, but not CD8+ T cells. Cell-based aAPCs can effectively expand cytolytic CD8+ cells, but optimal costimulatory signals have not been defined. 4-1BB, a costimulatory molecule expressed by a minority of resting CD8+ T cells, is transiently up-regulated by all CD8+ T cells following activation. We compared expansion of human cytolytic CD8+ T cells using cell-based aAPCs providing costimulation via 4-1BB vs CD28. Whereas anti-CD3/anti-CD28 aAPCs mostly expand naive cells, anti-CD3/4-1BBL aAPCs preferentially expand memory cells, resulting in superior enrichment of Ag-reactive T cells which recognize previously primed Ags and efficient expansion of electronically sorted CD8+ populations reactive toward viral or self-Ags. Using HLA-A2-Fc fusion proteins linked to 4-1BBL aAPCs, 3-log expansion of Ag-specific CD8+ CTL was induced over 14 days, whereas similar Ag-specific CD8+ T cell expansion did not occur using HLA-A2-Fc/anti-CD28 aAPCs. Furthermore, when compared with cytolytic T cells expanded using CD28 costimulation, CTL expanded using 4-1BB costimulation mediate enhanced cytolytic capacity due, in part, to NKG2D up-regulation. These results demonstrate that 4-1BB costimulation is essential for expanding memory CD8+ T cells ex vivo and is superior to CD28 costimulation for generating Ag-specific products for adoptive cell therapy.

STUDY SELECTION: Two reviewers assessed studies using predetermined inclusion criteria. DATA EXTRACTION:One reviewer extracted data with review by a second. RESULTS:We included 18 studies in a network meta-analysis assessing relative expected rates of IH clearance associated with β-blockers and steroids. Oral propranolol had the largest mean estimate of expected clearance (95%; 95% Bayesian credible interval [BCI]: 88%-99%) relative to oral corticosteroids (43%, 95% BCI: 21%-66%) and control (6%, 95% BCI: 1%-11%). Strength of evidence (SOE) was high for propranolol's effects on reducing lesion size compared with observation/placebo. Corticosteroids demonstrated moderate effectiveness at reducing size/volume (moderate SOE for improvement in IH). SOE was low for effects of topical timolol versus placebo. LIMITATIONS:Methodologic limitations of available evidence may compromise SOE. Validity of meta-analytic estimates relies on the assumption of exchangeability among studies, conditional on effects of the intervention. Results rely on assumed lack of reporting bias. CONCLUSIONS:Propranolol is effective at reducing IH size compared with placebo, observation, and other treatments including steroids in most studies. Corticosteroids demonstrate moderate effectiveness at reducing IH size/volume. The meta-analysis estimates provide a relative ranking of anticipated rates of lesion clearance among treatments. Families and clinicians making treatment decisions should also factor in elements such as lesion size, location, number, and type, and patient and family preferences. Dr Chinnadurai contributed to the conceptualization and design of the original review and meta-analysis and helped assess studies, verify data, develop the analysis, and draft the initial manuscript; Dr Fonnesbeck contributed to the conceptualization and design of the original review and meta-analysis, conducted the metaanalysis, and helped verify data and draft the initial manuscript; Drs Likis and McPheeters contributed to the conceptualization and design of the original review and meta-analysis and helped assess studies, develop the analysis, and draft the initial manuscript; Drs Morad and Snyder contributed to the conceptualization and design of the original review and meta-analysis and helped assess studies, verify data, develop the analysis, and draft the initial manuscript; Ms Sathe contributed to the conceptualization and design of the original review and meta-analysis and helped evaluate studies, extract and verify data, develop the analysis, and draft the initial manuscript; and all authors approved the fi nal manuscript as submitted. Infantile hemangiomas (IH) are the most common tumors of childhood. IH are benign but possess potential for permanent local tissue damage, ulceration, infection, bleeding, functional impact, and pain. Because of historical inconsistencies in naming conventions, the true prevalence of IH is unclear, but it is estimated that they affect ∼4% to 5% of children, 1 with higher prevalence in females and Caucasians. 2,3 ...

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Background-Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a lifethreatening risk to oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis virtually eliminates the risk of infection; however, many patients cannot tolerate TMP-SMZ. We performed a retrospective analysis to determine the PCP breakthrough rate in pediatric oncology patients receiving intravenous pentamidine as second line PCP prophylaxis.

It has been highlighted that youth empowerment and participation are important principles for school health promotion. Despite this fact, children and youth are rarely given instruments to participate or to influence their situations and the environments in their schools. Photovoice is a method to increased empowerment and participation. Originally it was created as a community action research method based on Freire's critical pedagogy and feminist theory. The purpose of this study was to explore challenges and opportunities for applying photovoice in a school setting to support genuine participation. Together with teachers and students in an upper secondary school in Östersund's municipality in the north of Sweden, the photovoice method was field tested and modified to a classroom situation. The teachers and the students were interviewed about their experiences with the method. The results were interpreted by content analysis and showed that the teachers' capability to be facilitators and the students' possibility to make a difference for the school or the municipality were the most important factors to succeed with photovoice. The conclusions were that photovoice challenges schools and society to have a better structure for genuine participation if youth participation is seen as valuable.

The association of cancer and thrombosis has been known for nearly 150 years. Compared with patients without cancer, those with cancer have an increased risk of thrombosis and recurrent thrombosis. It is now well accepted that patients with idiopathic venous thromboembolism are also at increased risk of later being diagnosed with cancer. This is further confirmation of the intertwined nature of cancer and thrombosis. Although the mechanisms of this association are still under examination, much work has accrued over the past two decades to suggest an influence of thrombin on cancer biology. This review focuses on the important role of thrombin in cancer research; recent in vitro work illustrating the mechanisms by which thrombin may affect cancer angiogenesis, cell invasion, and enhanced tumor metastasis; and on clinical trials investigating the potential role of antithrombotics in cancer incidence and survival.KEYWORDS: Cancer, thromboembolism, hypercoagulability, thrombin, antithromboticThe connection between cancer and thrombosis was observed and described initially in the mid-19th century when Professor Armand Trousseau presented his observations to the New Sydenham Society in 1865. Professor Trousseau, being a very astute internist in Paris, was particularly impressed by the frequent occurrence of symptomatic migratory thrombophlebitis in his cancer patients, particularly those with gastrointestinal malignancies. It is the irony of medical history that he diagnosed his own thrombophlebitis and predicted his own death from gastric cancer. In fact, he died 6 months later with a gastroesophageal cancer, leaving us with a prescient eponymous syndrome that is ripe for exploitation intellectually, scientifically, and therapeutically.Subsequently, in the modern era of clinical research, it is now appreciated that at least 10 to 20% of individuals who develop idiopathic venous thromboembolism (VTE) will develop evidence of cancer within 2 years.1 The recent MEGA population-based casecontrol study revealed that cancer patients have sevenfold increased risk of developing venous thromboembolism over that of non-cancer patients.2 Interestingly, and pertinent to tumor biology, is the fact that these thrombotic complications occur most frequently in the first 3 months after diagnosis and are associated most commonly with those malignancies with distant metastases. 2Epidemiologic studies indicate that cancer patients have a threefold increased risk for recurrence over that of noncancer patients, and the death rate from cancer in the context of concurrent VTE is fourfold higher than that of cancer itself, and this increased likelihood of death rate is not related to the cancer or the VTE as independent risk factors.3 Although Trousseau hypothesized that VTE complications were more likely to occur with gastrointestinal (GI) adenocarcinomas, the assessment of hospital admissions actually indicates that the relative risk of

Purpose The purpose of this paper is to explore the evidence of interlinkages between Lean and sustainability among organisational leaders in the early stages of Lean implementation. Design/methodology/approach A multiple-site case study was conducted to study the connections between Lean and sustainable development during the implementation stages of a Lean practice. In-depth interviews were conducted with managers about their knowledge and understanding of the interlinkages between Lean and sustainable development. The findings were then used as an analytic frame to determine whether these interlinkages were present in the organisation. Findings Evidence of interlinkages between Lean and sustainable development was found; however, their presence was incomplete and inconsistent across clinics. Research limitations/implications Insights from the research can help organisations plan for the implementation of Lean practice, particularly when a sub-goal is to achieve sustainable development. Originality/value The study shows the importance of focussing on managers’ knowledge and understanding of the interlinkages between Lean and sustainable development when implementing Lean in order to utilise Lean’s full potential to achieve sustainability.

As performance indicators and outcomes measures become essential parts of doing business, providers of mental health services are developing and using a number of access measures. One that is being used with increasing frequency is service penetration. However, the lack of standard methods for calculating and reporting service penetration has made the comparison of penetration rates cross studies difficult. This article discusses the conceptualization and operationalization of service penetration. In addition, it presents an exploratory study of service penetration using data from the same persons using very different data sources; these data were collected during an evaluation of a Medicaid managed care system in Florida. The article offers recommendations for the use and reporting of service penetration rates.