Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients

Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

<p>Abstract</p> <p>Purpose</p> <p>An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.</p> <p>Patients and methods</p> <p>Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis.</p> <p>Results</p> <p>The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; <it>P </it>= .002).</p> <p>Conclusion</p> <p>Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.</p

Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Harmonic publication and citation counting: sharing authorship credit equitably – not equally, geometrically or arithmetically

Bibliometric counting methods need to be validated against perceived notions of authorship credit allocation, and standardized by rejecting methods with poor fit or questionable ethical implications. Harmonic counting meets these concerns by exhibiting a robust fit to previously published empirical data from medicine, psychology and chemistry, and by complying with three basic ethical criteria for the equitable sharing of authorship credit. Harmonic counting can also incorporate additional byline information about equal contribution, or the elevated status of a corresponding last author. By contrast, several previously proposed counting schemes from the bibliometric literature including arithmetic, geometric and fractional counting, do not fit the empirical data as well and do not consistently meet the ethical criteria. In conclusion, harmonic counting would seem to provide unrivalled accuracy, fairness and flexibility to the long overdue task of standardizing bibliometric allocation of publication and citation credit

A Path Toward the Use of Trail Users’ Tweets to Assess Effectiveness of the Environmental Stewardship Scheme: An Exploratory Analysis of the Pennine Way National Trail

Large and unofficial data sets, for instance those gathered from social media, are increasingly being used in geographical research and explored as decision support tools for policy development. Social media data have the potential to provide new insight into phenomena about which there is little information from conventional sources. Within this context, this paper explores the potential of social media data to evaluate the aesthetic management of landscape. Specifically, this project utilises the perceptions of visitors to the Pennine Way National Trail, which passes through land managed under the Environmental Stewardship Scheme (ESS). The method analyses sentiment in trail users’ public Twitter messages (tweets) with the aim of assessing the extent to which the ESS maintains landscape character within the trail corridor. The method demonstrates the importance of filtering social media data to convert it into useful information. After filtering, the results are based on 161 messages directly related to the trail. Although small, this sample illustrates the potential for social media to be used as a cheap and increasingly abundant source of information. We suggest that social media data in this context should be seen as a resource that can complement, rather than replace, conventional data sources such as questionnaires and interviews. Furthermore, we provide guidance on how social media could be effectively used by conservation bodies, such as Natural England, which are charged with the management of areas of environmental value worldwide

Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1beta

Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.Alice C-H. Chen, Yang Xi, Melanie Carroll, Helen L. Petsky, Samantha J. Gardiner, Susan J. Pizzutto, Stephanie T. Yerkovich, Katherine J. Baines, Peter G. Gibson, Sandra Hodge, Ian B. Masters, Helen M. Buntain, Anne B. Chang and John W. Upha

Factors affecting the disclosure of diabetes by ethnic minority patients: a qualitative study among Surinamese in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Diabetes and related complications are common among ethnic minority groups. Community-based social support interventions are considered promising for improving diabetes self-management. To access such interventions, patients need to disclose their diabetes to others. Research on the disclosure of diabetes in ethnic minority groups is limited. The aim of our study was to explore why diabetes patients from ethnic minority populations either share or do not share their condition with people in their wider social networks.</p> <p>Methods</p> <p>We conducted a qualitative study using semi-structured interviews with 32 Surinamese patients who were being treated for type 2 diabetes by general practitioners in Amsterdam, the Netherlands.</p> <p>Results</p> <p>Most patients disclosed their diabetes only to very close family members. The main factor inhibiting disclosure to people outside this group was the Surinamese cultural custom that talking about disease is taboo, as it may lead to shame, gossip, and social disgrace for the patient and their family. Nevertheless, some patients disclosed their diabetes to people outside their close family circles. Factors motivating this decision were mostly related to a need for facilities or support for diabetes self-management.</p> <p>Conclusions</p> <p>Cultural customs inhibited Surinamese patients in disclosing their diabetes to people outside their very close family circles. This may influence their readiness to participate in community-based diabetes self-management programmes that involve other groups. What these findings highlight is that public health researchers and initiatives must identify and work with factors that influence the disclosure of diabetes if they are to develop community-based diabetes self-management interventions for ethnic minority populations.</p

Collaboration and knowledge exchange between scholars in Britain and the empire, 1830–1914

In recent years there has been a growing interest among historians in the British Empire as a space of knowledge production and circulation. Much of this work assumes that scholarly cooperation and collaboration between individuals and institutions within the Empire had the effect (and often also the aim) of strengthening both imperial ties and the idea of empire. This chapter argues, however, that many examples of scholarly travel, exchange, and collaboration were undertaken with very different goals in mind. In particular, it highlights the continuing importance of an ideal of scientific internationalism, which stressed the benefits of scholarship for the whole of humanity and prioritized the needs and goals of individual academic and scientific disciplines. As the chapter shows, some scholars even went on to develop nuanced critiques of the imperial project while using the very structures of empire to further their own individual, disciplinary and institutional goals