Education setting-based health promotion in New Zealand: evaluating the wellbeing and vitality in education (WAVE) programme.

Wellbeing and vitality in education (WAVE) is an education setting based health promotion initiative in South Canterbury, New Zealand. A mixed method approach was used for assessing change over time. Over ninety percent of education settings (94%) were participating in WAVE (n = 95). A total of 73 education settings completed the questionnaire at both baseline and follow-up. Evaluation of the WAVE programme shows that a robust partnership between health and education sectors can provide the basis for high levels of participation and significant changes in practice across all levels of education and a whole province. Evaluation results included that professional development for staff in some health related topics had improved. There was evidence of increasing partnerships between schools and community. Teachers had become role models for health messages and students had taken on leadership roles. Although the approach was based on health promoting schools literature, early engagement with education settings allowed the development of a local programme and branding. The overall outcome of WAVE has been a culture change in South Canterbury, where promoting the health of students, staff and families is becoming part of normal business for education settings. The results provide reason for optimism regarding the careful use of a health promoting schools framework, working in partnership with a range of stakeholders towards improving the health and subsequent life chances of young people.

Broadband longwave radio remote sensing instrumentation.

We present the performance characteristics of a high-sensitivity radio receiver for the frequency band 0.5-470 kHz, known as the Low Frequency Atmospheric Weather Electromagnetic System for Observation, Modeling, and Education, or LF AWESOME. The receiver is an upgraded version of the VLF AWESOME, completed in 2004, which provided high sensitivity broadband radio measurements of natural lightning emissions, transmitting beacons, and radio emissions from the near-Earth space environment. It has been deployed at many locations worldwide and used as the basis for dozens of scientific studies. We present here a significant upgrade to the AWESOME, in which the frequency range has been extended to include the LF and part of the medium frequency (MF) bands, the sensitivity improved by 10-25 dB to be as low as 0.03 fT/ Hz , depending on the frequency, and timing error reduced to 15-20 ns range. The expanded capabilities allow detection of radio atmospherics from lightning strokes at global distances and multiple traverses around the world. It also allows monitoring of transmitting beacons in the LF/MF band at thousands of km distance. We detail the specification of the LF AWESOME and demonstrate a number of scientific applications. We also describe and characterize a new algorithm for minimum shift keying demodulation for VLF/LF transmitters for ionospheric remote sensing applications.

The tobacco endgame: The neglected role of place and environment.

An increasing number of countries across the world are planning for the eradication of the tobacco epidemic. The actions necessary to realise this ambition have been termed the tobacco endgame. The focus of this paper is on the intersection between the tobacco endgame with place, a neglected theme in recent academic and policy debates. We begin with an overview of the key themes in the literature on endgame strategies before detailing the international landscape of engame initiatives, paying particular attention to the opportunities and challenges of endgame strategies in low and middle income countries. Finally, we critically assess the current endgame debates and suggest a novel agenda for integrating geographical perspectives into research on the endgame that provides enhanced understanding of the challenges associated with this important global health vision.

Comparative Proteomic Analysis of Whole-Gut Lavage Fluid and Pancreatic Juice Reveals a Less Invasive Method of Sampling Pancreatic Secretions.

OBJECTIVES: There are currently no reliable, non-invasive screening tests for pancreatic ductal adenocarcinoma. The fluid secreted from the pancreatic ductal system ("pancreatic juice") has been well-studied as a potential source of cancer biomarkers. However, it is invasive to collect. We recently observed that the proteomic profile of intestinal effluent from the bowel in response to administration of an oral bowel preparation solution (also known as whole-gut lavage fluid, WGLF) contains large amounts of pancreas-derived proteins. We therefore hypothesized that the proteomic profile is similar to that of pancreatic juice. In this study, we compared the proteomic profiles of 77 patients undergoing routine colonoscopy with the profiles of 19 samples of pure pancreatic juice collected during surgery. METHODS: WGLF was collected from patients undergoing routine colonoscopy, and pancreatic juice was collected from patients undergoing pancreatic surgery. Protein was isolated from both samples using an optimized method and analyzed by LC-MS/MS. Identified proteins were compared between samples and groups to determine similarity of the two fluids. We then compared our results with literature reports of pancreatic juice-based studies to determine similarity. RESULTS: We found 104 proteins in our pancreatic juice samples, of which 90% were also found in our WGLF samples. The majority (67%) of the total proteins found in the WGLF were common to pancreatic juice, with intestine-specific proteins making up a smaller proportion. CONCLUSIONS: WGLF and pancreatic juice appear to have similar proteomic profiles. This supports the notion that WGLF is a non-invasive, surrogate bio-fluid for pancreatic juice. Further studies are required to further elucidate its role in the diagnosis of pancreatic cancer.

mRNA detection in living cells: A next generation cancer stem cell identification technique.

Cancer stem cells (CSC) are a distinct subpopulation within a tumor shown to drive tumor progression, metastasis, and recurrence. A review of the literature reveals poor consensus, with the use of a wide variety of surface markers and functional assays to identify and isolate cancer stem cells. Utilizing a novel technology that enables live-cell mRNA quantitation, we have demonstrated the ability to identify and sort viable CSC based on markers associated with stemness in pluripotent cells. Fresh tumor samples from a variety of cancer types were examined by flow cytometry for Nanog expression. Levels of CSC detected ranged from 6% to 19%. This method of CSC detection was cross-validated with other commonly used surface markers with good correlation. Matrigel invasion assays confirmed that CSC isolated using this method are both highly motile and invasive. This approach simplifies the process of identifying viable CSC from fresh tumor tissue, providing a level of accuracy not previously available. This method may also provide a valuable tool for screening and validating new CSC biomarkers.

Improved rate of pancreatic fistula after distal pancreatectomy: parenchymal division with the use of saline-coupled radiofrequency ablation.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most common significant complication after distal pancreatectomy (DP) and results in substantial morbidity. Many different methods are available to divide the pancreatic parenchyma and achieve stump closure, but demonstrating an improvement in the incidence of POPF has been difficult. METHODS: A single-institution, retrospective review was conducted to evaluate all hand-assisted laparoscopic DP performed from October 2008 to July 2011 utilizing saline-coupled radiofrequency ablation (RFA) as the exclusive method of achieving division of the pancreatic parenchyma and closure of the proximal pancreatic remnant. All significant complications within the perioperative period were noted. RESULTS: Thirty-four patients met the criteria for inclusion in the study. One patient was lost to follow-up and thus excluded. Three patients (9.1%) demonstrated a POPF; two were treated with prolonged placement of the intraoperative drain (grade A: 6.1%) and the third was treated with endoscopic cystogastrostomy (grade C: 3.0%). One other significant complication (3.0%) of a perforated gastric ulcer that required partial gastrectomy occurred. CONCLUSIONS: The use of saline-coupled RFA alone for pancreatic parenchymal division and closure after DP is safe and effective. This study found an overall significant complication rate of 6.1%, and a rate of clinically significant POPF of 3.0%.

I can't get my husband to go and have a colonoscopy: gender and screening for colorectal cancer.

It is anticipated that a colorectal cancer (CRC) screening programme will be introduced in New Zealand making it the first screening programme in this country to include both males and females. In-depth interviews were carried out with 80 participants (53 females and 27 males) about their knowledge and attitudes to screening programmes in general, as well as their understanding and perceptions of CRC screening in particular. The study highlighted the perceived marginalization of men's health with a sense that women had advocated for, and therefore monopolized, screening while men's health had been left unattended. There were also perceptions of women's responsibility for ensuring men's access to health services. There are arguments that such perceptions disempower or 'infantalize' men which have no long term benefits. While health is perceived as being a feminine matter, it may be difficult to encourage men to engage in preventative behaviours, such as taking up the offer of screening. This article also highlights the heterogeneity of men, where different performances of masculinities were presented. A stereotypical 'staunch' or 'macho image' discourse was evident in some of the interviews where much emphasis was on maintaining and controlling bodily boundaries. Letting the barrier of embodied 'staunchness' down to access health services is a threat to identity. What is required for successful implementation of the CRC screening programme is a normalization of men's health help-seeking, taking into account the fact that men are not homogenous. Studies in relation to men's health need to attend to cultural diversity which is likely to present a challenge to individualism. Critical studies of men would be enhanced by more engagement with the work of black male scholars.

What do specialists and GPs think about the introduction of colorectal cancer screening? A qualitative study.

AIM: To explore the views of GPs and specialists on colorectal cancer (CRC) screening. METHODS: Qualitative study using semi-structured interviews of 15 GPs and 11 specialists investigating views on the proposed introduction of CRC screening in New Zealand. RESULTS: Both GPs and specialists in this study, whilst agreeing on the overall merit of a population screening programme for CRC in New Zealand, argued that there were not sufficient resources to warrant the implementation of such a programme. There was also little support, especially by the GPs, for the faecal occult blood test, which is likely to be the screening test if implemented. CONCLUSIONS: The concerns of GPs and specialists need to be addressed if a screening programme for CRC is introduced in New Zealand. GPs undoubtedly would have to be the advocates of this programme to their patients and therefore they will have to be convinced of the value of this exercise.

Solid-pseudopapillary tumor: a report of three cases in adult males diagnosed utilizing three different modalities.

Solid-pseudopapillary tumor of the pancreas is a rare neoplasm of uncertain origin with low malignant potential and often indolent behavior occurring predominantly in adolescent and young women. Here we report the cases of three adult males with pancreatic masses, one with metastasis, diagnosed as solid-pseudopapillary tumor by cytology, electron microscopy (EM), and routine histology. This neoplasm is uncommon in both males and adults and uncommonly metastasizes. The cases reported emphasize the utility of different diagnostic modalities, and here we review the diagnostic features by cytology, EM, and routine histology to correctly characterize this neoplasm. It is extremely important to correctly diagnose this indolent neoplasm due to the excellent prognosis with surgical resection.

Current surgical management of melanoma.

The surgical management of melanoma has changed dramatically over the last few decades. Through the development and conduction of well-designed, prospective, randomized trials, we have been able to refine the way that we surgically manage patients with melanoma. Indeed, many important issues have been addressed through such trials: the proper surgical margins for the primary melanoma, utility of the elective lymph node dissection and the role for selective lymphadenectomy, to name a few. This review will also discuss what we have learned from past clinical trials and address several issues with regards to where we are going in the future.

Sequential immune escape and shifting of T cell responses in a long-term survivor of melanoma.

Immune-mediated control of tumors may occur, in part, through lysis of malignant cells by CD8(+) T cells that recognize specific Ag-HLA class I complexes. However, tumor cell populations may escape T cell responses by immune editing, by preventing formation of those Ag-HLA complexes. It remains unclear whether the human immune system can respond to immune editing and recognize newly arising escape variants. We report an example of shifting immune responses to escape variants in a patient with sequential metastases of melanoma and long-term survival after surgery alone. Tumor cells in the first metastasis escaped immune recognition via selective loss of an HLA haplotype (HLA-A11, -B44, and -Cw17), but maintained expression of HLA-A2. In the second metastasis, immune escape from an immunodominant MART-1-specific T cell response was mediated by HLA class I down-regulation, resulting in a failure to present this epitope, but persistent presentation of a tyrosinase-derived epitope. Consequent to this modification in tumor Ag presentation, the dominant CTL response shifted principally toward a tyrosinase-targeted response, even though tyrosinase-specific CTL had been undetectable during the initial metastatic event. Thus, in response to immune editing of tumor cells, a patient's spontaneous T cell response adapted, gaining the ability to recognize and to lyse "edited" tumor targets. The observation of both immune editing and immune adaptation in a patient with long-term survival after surgery alone demonstrates an example of immune system reactivity to counteract the escape mechanism(s) developed by tumor cells, which may contribute to the clinical outcome of malignant disease.

Competition among peptides in melanoma vaccines for binding to MHC molecules.

The effectiveness of peptide-based cancer vaccines depends on the ability of peptides to bind to MHC molecules on the surface of antigen-presenting cells, where they reconstitute epitopes for cytotoxic T lymphocytes (CTLs). Multivalent vaccines have advantages over single-peptide vaccines; however, peptides may compete for binding to the same MHC molecules. In particular, it is possible that peptides with high affinity for MHC molecules prevent the binding of lower-affinity peptides. However, only small numbers of peptide/MHC complexes per cell are required for CTL recognition. Thus, the authors hypothesized that competition of peptides for MHC binding would not significantly reduce CTL recognition of individual peptides within a multiple-peptide mixture, and this hypothesis was tested by a series of experiments performed in vitro. In multiple experiments, two peptides with different affinities for HLA-A*0201 molecules were mixed at various concentrations and pulsed onto HLA-A2 cells, which were then evaluated for susceptibility to lysis by HLA-A*0201-restricted CTLs. CTL recognition of the melanoma peptides gp100(154-162) (KTWGQYWQV), gp100(280-288) (YLEPGPVTA), and tyrosinase(369-377D) (YMDGTMSQV) was maintained even when target cells were co-pulsed with equimolar concentrations of peptides with comparable or higher affinity for HLA-A2. In some cases, CTL recognition was maintained even when the higher-affinity peptide was present at concentrations several orders of magnitude higher than the target peptide. In addition, CTLs generated by in vitro stimulation with a peptide mixture developed reactivity to three different peptides, at a level comparable to that obtained by stimulation with each individual peptide separately. These data suggest that CTLs can respond to multiple peptides presented on the same antigen-presenting cells and justify further investigation, in clinical trials, of multiple-peptide cancer vaccines.

Infectious complications after hepatic resection.

The purpose of this study was to assess the characteristics of surgical infections after hepatic resection (HR) to identify factors accounting for increased postoperative mortality. Advances in operative technique and care have decreased morbidity and mortality after HR. However, infections after HR continue to be a major contributor to postoperative morbidity and mortality. All HR done during a 7-year period were analyzed and compared to our prospective surgical infection database. Factors contributing to infectious complications and mortality were identified. HR (n = 207) were performed with an overall mortality of 5.8 per cent. Nine patients (3.3%) had 18 infections; 6 (60%) had multiple infection sites, most commonly the peritoneum, blood, or wound. Three infected patients died. Lung and line infections occurred in 2 (67%) infection-related deaths. No single comorbidity increased postoperative infection risk, but an average of 6.7 comorbid conditions were present. All infection-related deaths were associated with ventilator-dependence. All infection-related deaths occurred after resection of a mean of four segments. Additional procedures at the time of HR, operative drains, or transfusion requirements did not impact infectious complications or mortality. Methicillin-resistant Staphylococcus sp. was isolated in all infection-related deaths. The mean time from HR to initiation of treatment was 8 days for infection survivors and 13.3 days for infection-related deaths. Infectious mortality after HR remains significant. Contributing risk factors are advanced age, multiple comorbid conditions, and extent of HR. Ventilator-dependence and delays in antibiotic therapy were associated with infectious mortality. Although gram-negative enteric infections were more common, abdominal, lung, and line infections with gram-positive cocci had higher associated mortality; especially when antibiotic resistant strains were present.

Preventing the spontaneous modification of an HLA-A2-restricted peptide at an N-terminal glutamine or an internal cysteine residue enhances peptide antigenicity.

The p68-derived peptide, QIVDVCHDV, was identified by a reverse immunology approach as capable of reconstituting an epitope recognized by the melanoma-reactive cytotoxic T lymphocyte (CTL) line VMM5. The peptide has not been demonstrated definitively on the cell surface by mass spectrometry; thus, it is not yet considered appropriate for use in human melanoma vaccines. Interestingly, however, the antigenicity of this peptide was affected by spontaneous modifications at two distinct residues. Spontaneous modification of the QIVDVCHDV peptide can occur at the cysteine residue at position 6 or at the N-terminal glutamine residue, and both modifications dramatically affect CTL recognition. Avoidance of an acidic environment prevents the conversion of the N-terminal glutamine residue to pyroglutamic acid, a conversion that inhibits binding of the peptide to HLA-A2 and diminishes recognition by CTLs. Substitution of asparagine for the N-terminal glutamine and substitution of serine for the cysteine were shown to enhance the binding of the peptide to HLA-A2 and to enhance the recognition of the peptide by CTLs. These findings suggest general strategies for enhancing the antigenicity of other peptides containing similar amino acids in their sequence.

Identification of novel and widely expressed cancer/testis gene isoforms that elicit spontaneous cytotoxic T-lymphocyte reactivity to melanoma.

Multiple isoforms (TAG-1, TAG-2a, TAG-2b, and TAG-2c) of a novel cancer/testis antigen gene have been identified and are expressed in 84-88% of melanoma cell lines tested. The tumor antigen (TAG) genes are also expressed in K562, a myelogenous leukemia cell line, and they have homology to two chronic myelogenous leukemia-derived clones and a hepatocellular carcinoma clone in the human expressed sequence tags (EST) database, thus indicating that their expression is not restricted to melanomas. In contrast to the fact that many cancer/testis antigens are poorly immunogenic, the TAG-derived peptide, RLSNRLLLR, is recognized by HLA-A3-restricted, melanoma-specific CTLs that were obtained from a melanoma patient with spontaneous reactivity to the peptide. Unlike most cancer/testis antigen genes which are located on the X chromosome, the TAG genes are located on chromosome 5. The genes have the additional unusual features of being coded for in an open reading frame that is initiated by one of three nonstandard initiation codons, and the sequence coding the RLSNRLLLR peptide crosses an exon-exon boundary. The properties of the TAG antigens indicate that they are excellent vaccine candidates for the treatment of melanoma and perhaps other cancers.

Identification of a shared epitope recognized by melanoma-specific, HLA-A3-restricted cytotoxic T lymphocytes.

We previously established a melanoma-reactive cytotoxic T lymphocyte (CTL) line that recognizes multiple epitopes in the context of HLA-A3. To increase the number of peptides available for use in a vaccine for the treatment of melanoma, we identified one of these epitopes, SQNFPGSQK, through a combination of epitope reconstitution experiments and mass spectrometry. The SQNFPGSQK peptide was also found to be associated with HLA-A3 on an additional melanoma tumor line, thus indicating that the peptide is not unique to the melanoma tumor line from which it was isolated and thus, unlikely to arise through a mutational event. Although the protein origin of SQNFPGSQK has yet to be established, the shared nature of this epitope and the fact that it elicits a natural immune response indicates that it warrants further study to determine its usefulness as a vaccine component for the treatment of melanoma. The peptide may also be useful as a research tool for evaluating spontaneous anti-tumor immune responses in patients with melanoma.