Human Leukocyte Antigen Class I and II Alleles and Overall Survival in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA) genes and tumor necrosis factor (TNF), has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects of HLA class I (A, B, and C), class II DRB1 alleles, and the ancestral haplotype (AH) 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A) on overall survival (OS) among patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in a population-based study of non-Hodgkin lymphoma. During a median followup of 89 months, 31% (52 of 166) DLBCL and 28% (46 of 165) FL patients died. Using multivariate Cox regression models, we observed statistically significant associations between genetic variants and survival: HLA-Cw*07:01 was associated with poorer OS among DLBCL patients (Hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.01–3.05); HLA-A*01:01 was associated with poorer OS (HR = 2.23, 95% CI = 1.24–4.01), and HLA-DRB1*13 (HR = 0.12, 95% CI = 0.02–0.90) and HLA-B Bw4 (HR = 0.36, 95% CI = 0.20–0.63) with better OS among FL patients. These results support a role for HLA in the prognosis of DLBCL and FL and represent a promising class of prognostic factors that warrants further evaluation

Coupled-channels analysis of the 16^{{\bf 16}}O+208^{{\bf 208}}Pb fusion barrier distribution

Analyses using simplified coupled-channels models have been unable to describe the shape of the previously measured fusion barrier distribution for the doubly magic $^{16}$O+$^{208}$Pb system. This problem was investigated by re-measuring the fission excitation function for $^{16}$O+$^{208}$Pb with improved accuracy and performing more exact coupled-channels calculations, avoiding the constant-coupling and first-order coupling approximations often used in simplified analyses. Couplings to the single- and 2-phonon states of $^{208}$Pb, correctly taking into account the excitation energy and the phonon character of these states, particle transfers, and the effects of varying the diffuseness of the nuclear potential, were all explored. However, in contrast to other recent analyses of precise fusion data, no satisfactory simultaneous description of the shape of the experimental barrier distribution and the fusion cross-sections for $^{16}$O+$^{208}$Pb was obtained.Comment: RevTex, 29 pages, 7 postscript figures, to appear in PR

Multidisciplinary teams, and parents, negotiating common ground in shared-care of children with long-term conditions: A mixed methods study

Background: Limited negotiation around care decisions is believed to undermine collaborative working between parents of children with long-term conditions and professionals, but there is little evidence of how they actually negotiate their respective roles. Using chronic kidney disease as an exemplar this paper reports on a multi-method study of social interaction between multidisciplinary teams and parents as they shared clinical care. Methods. Phases 1 and 2: a telephone survey mapping multidisciplinary teams' parent-educative activities, and qualitative interviews with 112 professionals (Clinical-psychologists, Dietitians, Doctors, Nurses, Play-specialists, Pharmacists, Therapists and Social-workers) exploring their accounts of parent-teaching in the 12 British children's kidney units. Phase 3: six ethnographic case studies in two units involving observations of professional/parent interactions during shared-care, and individual interviews. We used an analytical framework based on concepts drawn from Communities of Practice and Activity Theory. Results: Professionals spoke of the challenge of explaining to each other how they are aware of parents' understanding of clinical knowledge, and described three patterns of parent-educative activity that were common across MDTs: Engaging parents in shared practice; Knowledge exchange and role negotiation, and Promoting common ground. Over time, professionals had developed a shared repertoire of tools to support their negotiations with parents that helped them accomplish common ground during the practice of shared-care. We observed mutual engagement between professionals and parents where a common understanding of the joint enterprise of clinical caring was negotiated. Conclusions: For professionals, making implicit knowledge explicit is important as it can provide them with a language through which to articulate more clearly to each other what is the basis of their intuition-based hunches about parents' support needs, and may help them to negotiate with parents and accelerate parents' learning about shared caring. Our methodology and results are potentially transferrable to shared management of other conditions. © 2013 Swallow et al.; licensee BioMed Central Ltd

Radical nostalgia, progressive patriotism and Labour's 'English problem'

‘Progressive patriots’ have long argued that Englishness can form the basis of a transformative political project, whether based on an historic tradition of resistance to state power or an open and cosmopolitan identity. However, this article suggests that the politics of Englishness present a number of specific dilemmas for Labour. First the historical narrative of a radical tradition in British history is not straightforwardly English and cannot easily be used to support a competitive politics of nationhood, in the way that disaffected English identifiers might desire. Second, the deliberately alternative nature of this ‘radical nostalgic’ narrative makes it an unlikely basis for a unifying national story. It is also at odds with Labour’s status as a successful party of government, committed to using the power of the British state, rather than opposing it. Finally, while ‘everyday Englishness’ may well align with core Labour values and be less socially conservative, intolerant or racially exclusive than it is often described, its very nature as an everyday practice, rather than a political identity makes it difficult for Labour to co-opt

Identification and evaluation of epidemic prediction and forecasting reporting guidelines : a systematic review and a call for action

NGR reports funding by NIGMS grant R35GM119582. BMA is supported by Bill and Melinda Gates Foundation through the Global Good Fund. SP and IMB were funded by the Armed Forces Health Surveillance Branch (GEIS: P0116_19_WR_03.11).Introduction: High quality epidemic forecasting and prediction are critical to support response to local, regional and global infectious disease threats. Other fields of biomedical research use consensus reporting guidelines to ensure standardization and quality of research practice among researchers, and to provide a framework for end-users to interpret the validity of study results. The purpose of this study was to determine whether guidelines exist specifically for epidemic forecast and prediction publications. Methods: We undertook a formal systematic review to identify and evaluate any published infectious disease epidemic forecasting and prediction reporting guidelines. This review leveraged a team of 18 investigators from US Government and academic sectors. Results: A literature database search through May 26, 2019, identified 1467 publications (MEDLINE n = 584, EMBASE n = 883), and a grey-literature review identified a further 407 publications, yielding a total 1777 unique publications. A paired-reviewer system screened in 25 potentially eligible publications, of which two were ultimately deemed eligible. A qualitative review of these two published reporting guidelines indicated that neither were specific for epidemic forecasting and prediction, although they described reporting items which may be relevant to epidemic forecasting and prediction studies. Conclusions: This systematic review confirms that no specific guidelines have been published to standardize the reporting of epidemic forecasting and prediction studies. These findings underscore the need to develop such reporting guidelines in order to improve the transparency, quality and implementation of epidemic forecasting and prediction research in operational public health.Publisher PDFPeer reviewe

Identification and Evaluation of Epidemic Prediction and Forecasting Reporting Guidelines: A Systematic Review and a Call for Action

INTRODUCTION: High quality epidemic forecasting and prediction are critical to support response to local, regional and global infectious disease threats. Other fields of biomedical research use consensus reporting guidelines to ensure standardization and quality of research practice among researchers, and to provide a framework for end-users to interpret the validity of study results. The purpose of this study was to determine whether guidelines exist specifically for epidemic forecast and prediction publications. METHODS: We undertook a formal systematic review to identify and evaluate any published infectious disease epidemic forecasting and prediction reporting guidelines. This review leveraged a team of 18 investigators from US Government and academic sectors. RESULTS: A literature database search through May 26, 2019, identified 1467 publications (MEDLINE n = 584, EMBASE n = 883), and a grey-literature review identified a further 407 publications, yielding a total 1777 unique publications. A paired-reviewer system screened in 25 potentially eligible publications, of which two were ultimately deemed eligible. A qualitative review of these two published reporting guidelines indicated that neither were specific for epidemic forecasting and prediction, although they described reporting items which may be relevant to epidemic forecasting and prediction studies. CONCLUSIONS: This systematic review confirms that no specific guidelines have been published to standardize the reporting of epidemic forecasting and prediction studies. These findings underscore the need to develop such reporting guidelines in order to improve the transparency, quality and implementation of epidemic forecasting and prediction research in operational public health

Risk, risk factors and surveillance of subsequent malignant neoplasms in childhood cancer survivors: a review

Subsequent malignant neoplasms (SMNs) in childhood cancer survivors cause substantial morbidity and mortality. This review summarizes recent literature on SMN epidemiology, risk factors, surveillance, and interventions. Survivors of childhood cancer experience long-term increased SMN risk compared with the general population, with a greater than twofold increased solid tumor risk extending beyond age 40 years. There is a dose-dependent increased risk for solid tumors after radiotherapy, with the highest risks for tumors occurring in or near the treatment field (eg, greater than fivefold increased risk for breast, brain, thyroid, skin, bone, and soft tissue malignancies). Alkylating and anthracycline chemotherapies increase the risk for development of several solid malignancies in addition to acute leukemia/myelodysplasia, and these risks may be modified by other patient characteristics, such as age at exposure and, potentially, inherited genetic susceptibility. Strategies for identifying survivors at risk and initiating long-term surveillance have improved and interventions are underway to improve knowledge about late-treatment effects among survivors and caregivers. Better understanding of treatment-related risk factors and genetic susceptibility holds promise for refining surveillance strategies and, ultimately, upfront cancer therapies

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Author Correction: A consensus-based transparency checklist.

An amendment to this paper has been published and can be accessed via a link at the top of the paper