Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically ...associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.
The Apex of Hipster XML GeekDOM Siemens, Lynne; Siemens, Ray; Wen, Hefeng (Eddie) ...
Journal of the Text Encoding Initiative,
06/2011, Letnik:
1
Journal Article
Recenzirano
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If the notion of the methodological commons is as centrally located as we believe it to be in any visualization accurately depicting the intellectual structure of the digital humanities and digital ...literary studies (McCarty 2005, 119), then so, too, must be the community itself whose members provide that which populates the commons. As an interdiscipline, humanities computing has always well-understood its methodologies; indeed, the digital humanities (of which digital literary studies is a part), more generally, have made a virtue of the way in which they render explicit and tangible the theoretical models that govern the representative and analytical endeavour of their fields via computational application. So, too, have those in the field understood and documented its formal structures and institutional manifestations, a chief example being the Text Encoding Initiative itself. Less explicitly rendered and less formally documented–though intuited by its chief practitioners and builders–is the exact nature of the community itself, its depth and breadth, its own centre and, perhaps more important in a field whose embrace of interdisciplinarity is far from self-serving, its periphery and those aspects of which promise to become central. This article presents work carried out in conjunction with the Text Encoding Initiative Consortium, a foundation of many digital literary studies projects, work that seeks to document the full nature of its community, from the institutional and research project groups that comprise the formal consortium at centre to those who appear on the other side of the easily-permeable periphery that separates it from the centre, largely individual practitioners in areas hitherto not closely identified with the digital humanities but clearly sharing methods and tools, thus suggesting their place in the same communities of practice, as they are members of the same methodological commons. This methodological approach is drawn from marketing and organizational behavior, manifest in social networking, in the study of viral marketing campaigns conducted in online environments. The method for this work was centred around a viral marketing experiment designed to showcase the TEI and novel ways that it can be used to encode different kinds of text. At the heart of the experiment was a Bob Dylan song and its associated video which incorporated text; encoded text was overlaid and the video was posted to YouTube and a blog with links to the TEI website with analysis of traffic patterns carried out.
As the amount of scholarly material published in digital form increases, there is growing pressure on content producers to identify the needs of expert readers and to create online tools that satisfy ...their requirements. Based on the results of a study conducted by the Public Knowledge Project and introduced at Digital Humanities 2006 (Siemens, Willinsky and Blake), continued and augmented since, this paper discusses the reactions of Humanities Computing scholars and graduate students to using a set of online reading tools. The results of our study reveal both the potential strengths and perceived weaknesses of online reading environments. Understanding how users read and evaluate research materials, anticipating users’ expectations of the reading tools and resources, and addressing user concerns about the availability of online material will lead to improvements in the design and features of online publishing.
The Apex of Hipster XML GeekDOM Siemens, Lynne; Siemens, Ray; Wen, Hefeng (Eddie) ...
Journal of the Text Encoding Initiative,
06/2011
Issue 1
Journal Article
Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and ...radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.
Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.
Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.
The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.
Early and frequent antenatal care attendance during pregnancy is important to identify and mitigate risk factors in pregnancy and to encourage women to have a skilled attendant at childbirth. ...However, many pregnant women in sub-Saharan Africa start antenatal care attendance late, particularly adolescent pregnant women. Therefore they do not fully benefit from its preventive and curative services. This study assesses the timing of adult and adolescent pregnant women's first antenatal care visit and identifies factors influencing early and late attendance.
The study was conducted in the Ulanga and Kilombero rural Demographic Surveillance area in south-eastern Tanzania in 2008. Qualitative exploratory studies informed the design of a structured questionnaire. A total of 440 women who attended antenatal care participated in exit interviews. Socio-demographic, social, perception- and service related factors were analysed for associations with timing of antenatal care initiation using regression analysis.
The majority of pregnant women initiated antenatal care attendance with an average of 5 gestational months. Belonging to the Sukuma ethnic group compared to other ethnic groups such as the Pogoro, Mhehe, Mgindo and others, perceived poor quality of care, late recognition of pregnancy and not being supported by the husband or partner were identified as factors associated with a later antenatal care enrolment (p < 0.05). Primiparity and previous experience of a miscarriage or stillbirth were associated with an earlier antenatal care attendance (p < 0.05). Adolescent pregnant women started antenatal care no later than adult pregnant women despite being more likely to be single.
Factors including poor quality of care, lack of awareness about the health benefit of antenatal care, late recognition of pregnancy, and social and economic factors may influence timing of antenatal care. Community-based interventions are needed that involve men, and need to be combined with interventions that target improving the quality, content and outreach of antenatal care services to enhance early antenatal care enrolment among pregnant women.
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological ...cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here, we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4+ T cells, causing stem cell proliferation, differentiation, and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4+ T cells, demonstrating that HSPCs are not only passive receivers of immunological signals but also actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool.
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•HSPCs constitutively present antigens via MHC-II•Presentation of immunogenic antigens results in the activation of CD4+ T cells•Antigen presentation causes differentiation and depletion of immunogenic HSPCs•This prohibits the onset of HSC-derived leukemias presenting neoantigens via MHC-II
Haas and colleagues show that hematopoietic stem cells (HSCs) act as antigen-presenting cells. The presentation of immunogenic antigens triggers a bidirectional interaction with antigen-specific CD4+ T cells, resulting in the rapid exhaustion of diseased HSCs, thereby safeguarding the integrity of the stem cell pool.
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