Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections : Comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context

Background A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). Methods CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. Results Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. Conclusions WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided. Pediatr Pulmonol. 2012; 47:386-392. (C) 2011 Wiley Periodicals, Inc.

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/ cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer : a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)

Background: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. Patients and methods: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m 2, carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m 2, ifosfamide 3 g/m 2 and cisplatin 50 mg/m 2 or mitomycin 6 mg/ m 2, vinblastine 6 mg/m 2 and cisplatin 50 mg/m 2, respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. Results: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. Conclusions: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained. © 2006 European Society for Medical Oncology.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

Murray Valley Encephalitis

Outbreaks of an acute, severe, encephalitic illness, clinically similar to Japanese and St. Louis encephalitis, occurred in rural areas of southeastern Australia in 1917, 1918, 1922, 1925, 1951, and 1974[1,9,14-16] and in north and northwestern Australia in 1981, 1993, and 2000.[8,12,41] Approximately 420 cases were reported in these nine outbreaks.[41] They are thought to represent a single entity for which various names (Australian X disease, Murray Valley encephalitis, Australian encephalitis) have been used. Twenty-two cases were diagnosed in the 5 years between 2007 and 2011; three were fatal, and one of the fatalities occurred in a Canadian tourist on return from a holiday in northern Australia. Case-fatality rates, as high as 70 percent in the early years,[9,11] declined to 20 percent in the 1974 outbreak and have remained at about this level since then.[5,10,12] However, significant residual neurologic disability occurs in as many as 50 percent of survivors.[10,12] The presence of this disease in Papua New Guinea was confirmed in 1956.[20] The causative virus was transmitted to experimental animals as early as 1918,[6,11] although those strains could not be maintained. The definitive isolation and characterization of Murray Valley encephalitis virus in 1951[19] led to epidemiologic studies that suggested its survival in bird-mosquito cycles in northern Australia but not in the area of epidemic occurrence in southern Australia.[1] Murray Valley encephalitis is caused by Murray Valley encephalitis virus. In an effort to dissociate a disease from a specific locality, the term Australian encephalitis was proposed by residents of Murray Valley for the disease caused by Murray Valley encephalitis virus. Some researchers subsequently have attempted to expand the term Australian encephalitis to include encephalitis caused by any Australian arbovirus. Because the term Australian encephalitis has no scientific validity and is ambiguous, it should not be used.

bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non- small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role if bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-NO, 1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c- erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c- erbB-2-related immune response remains to be further investigated.

C. elegans RNA-dependent RNA polymerases rrf-1 and ego-1 silence Drosophila transgenes by differing mechanisms

Drosophila possesses the core gene silencing machinery but, like all insects, lacks the canonical RNA-dependent RNA polymerases (RdRps) that in C. elegans either trigger or enhance two major small RNA-dependent gene silencing pathways. Introduction of two different nematode RdRps into Drosophila showed them to be functional, resulting in differing silencing activities. While RRF-1 enhanced transitive dsRNA-dependent silencing, EGO-1 triggered dsRNA-independent silencing, specifically of transgenes. The strain w; da-Gal4; UAST-ego-1, constitutively expressing ego-1, is capable of silencing transgene including dsRNA hairpin upon a single cross, which created a powerful tool for research in Drosophila. In C. elegans, EGO-1 is involved in transcriptional gene silencing (TGS) of chromosome regions that are unpaired during meiosis. There was no opportunity for meiotic interactions involving EGO-1 in Drosophila that would explain the observed transgene silencing. Transgene DNA is, however, unpaired during the pairing of chromosomes in embryonic mitosis that is an unusual characteristic of Diptera, suggesting that in Drosophila, EGO-1 triggers transcriptional silencing of unpaired DNA during embryonic mitosis. © 2012 Springer Basel.

Identification and occupational stress : a stress-buffering perspective

Occupational stress research has consistently demonstrated many negative effects of work stressors on employee adjustment (i.e., job-related attitudes and health). Considerable literature also describes potential moderators of this relationship. While research has revealed that different workplace identifications can have significant positive effects on employee adjustment, it has neglected to investigate their potential stress-buffering effects. Based on identity theories, it was predicted that stress-buffering effects of different types of identifications (distal versus proximal) would be revealed when the identification type and employee adjustment outcome type (distal versus proximal) were congruent. Predictions were tested with an employee sample from five human service nonprofit organizations (N = 337). Hierarchical multiple regression analyses revealed that main and moderated effects relating to identification supported the notion that occupational stress would be reduced when there was congruence of distal and proximal identifications and distal and proximal outcome types. However, stress-buffering effects were also found for high identifiers and low identifiers that were not in line with hypotheses posing questions for the definitions of distal and proximal identifications. Findings are discussed in terms of theoretical and practical implications.

Geologic map of the Valley Mountain 15’ quadrangle, San Bernardino and Riverside Counties, California: U.S. Geological Survey Geologic Quadrangle Map GQ–1767, scale 1:62,500

The Valley Mountain 15’ quadrangle straddles the Pinto Mountain Fault, which bounds the eastern Transverse Ranges in the south against the Mojave Desert province in the north. The Pinto Mountains, part of the eastern Transverse Ranges in the south part of the quadrangle expose a series of Paleoproterozoic gneisses and granite and the Proterozoic quartzite of Pinto Mountain. Early Triassic quartz monzonite intruded the gneisses and was ductiley deformed prior to voluminous Jurassic intrusion of diorite, granodiorite, quartz monzonite, and granite plutons. The Jurassic rocks include part of the Bullion Mountains Intrusive Suite, which crops out prominently at Valley Mountain and in the Bullion Mountains, as well as in the Pinto Mountains. Jurassic plutons in the southwest part of the quadrangle are deeply denuded from midcrustal emplacement levels in contrast to supracrustal Jurassic limestone and volcanic rocks exposed in the northeast. Dikes inferred to be part of the Jurassic Independence Dike Swarm intrude the Jurassic plutons and Proterozoic rocks. Late Cretaceous intrusion of the Cadiz Valley Batholith in the northeast caused contact metamorphism of adjacent Jurassic plutonic rocks...

Intranasal immunization with C. muridarum major outer membrane protein (MOMP) and cholera toxin elicits local production of neutralising IgA in the prostate

Successful control of sexually transmitted diseases (STDs) through vaccination will require the development of vaccine strategies that target protective immunity to both the female and male reproductive tracts (MRT). In the male, the immune privileged nature of the male reproductive tract provides a barrier to entry of serum immunoglobulins into the male reproductive ducts, thereby preventing the induction of protective immunity using conventional injectable vaccination techniques. In this study we investigated the potential of intranasal (IN) immunization to elicit anti-chlamydial immunity in BALB/c male mice. Intranasal immunization with Chlamydia muridarum major outer membrane protein (MOMP) admixed with cholera toxin (CT) resulted in high levels of MOMP-specific IgA in prostatic fluids (PF) and MOMP-specific IgA-secreting cells in the prostate. Prostatic fluid IgA inhibited in vitro infection of McCoy cells with C. muridarum. Using RT-PCR we also show that mRNA for the polymeric immunoglobulin receptor (PIgR), which transports IgA across mucosal epithelia, is expressed only in the prostate but not in other regions of the male reproductive ducts upstream of the prostate. These data suggest that using intranasal immunization to target IgA to the prostate may protect males against STDs while at the same time maintaining the state of immune privilege within the MRT.

Differential expression of VEGF ligands and receptors in prostate cancer

BACKGROUND Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. METHODS The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. RESULTS Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. CONCLUSIONS These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer.

Book review: ‘Cornea. Color Atlas & Synopsis of Clinical Ophthalmology. Wills Eye Institute’, by C.J. Rapuano. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia 2012

This book is one in a series of seven atlases covering the ophthalmic sub-specialties: cornea, retina, glaucoma, oculoplastics, neuro-ophthalmology, uveitis and paediatrics. The author of Cornea and editor of the series is Christopher Rapuano, Attending Surgeon and Director of the Cornea Service at Wills Eye Hospital in Philadelphia, Pennsylvania, USA. In the introduction to the book, Rapuano states ‘The goal of this series is to provide an up-to-date clinical overview of the major areas of ophthalmology for students, residents and practitioners in all the healthcare professions’...

The first x-ray diffraction peak of water as a function of temperature in the range 4 – 63 °C

X-ray diffraction structure functions for water flowing in a 1.5 mm diameter siphon in the temperature range 4 – 63 °C were obtained using a 20 keV beam at the Australian Synchrotron. These functions were compared with structure functions obtained at the Advanced Light Source for a 0.5 mm thick sample of water in the temperature range 1 – 77 °C irradiated with an 11 keV beam. The two sets of structure functions are similar, but there are subtle differences in the shape and relative position of the two functions suggesting a possible differences between the structure of bulk and siphon water. In addition, the first structural peak (Q0) for water in a siphon, showed evidence of a step-wise increase in Q0 with increasing temperature rather than a smoothly varying increase. More experiments are required to investigate this apparent difference.

Incorporating anchored learning in a C# Intelligent Tutoring System

Learning programming is known to be difficult. One possible reason why students fail programming is related to the fact that traditional learning in the classroom places more emphasis on lecturing the material instead of applying the material to a real application. For some students, this teaching model may not catch their interest. As a result they may not give their best effort to understand the material given. Seeing how the knowledge can be applied to real life problems can increase student interest in learning. As a consequence, this will increase their effort to learn. Anchored learning that applies knowledge to solve real life problems may be the key to improving student performance. In anchored learning, it is necessary to provide resources that can be accessed by the student as they learn. These resources can be provided by creating an Intelligent Tutoring System (ITS) that can support the student when they need help or experience a problem. Unfortunately, there is no ITS developed for the programming domain that has incorporated anchored learning in its teaching system. Having an ITS that supports anchored learning will not only be able to help the student learn programming effectively but will also make the learning process more enjoyable. This research tries to help students learn C# programming using an anchored learning ITS named CSTutor. Role playing is used in CSTutor to present a real world situation where they develop their skills. A knowledge base using First Order Logic is used to represent the student's code and to give feedback and assistance accordingly.

Beyond actuality : locating an authentic hybridity between heterogeneous media in an installation art practice

Addressing possibilities for authentic combinations of diverse media within an installation setting, this research tested hybrid blends of the physical, digital and temporal to explore liminal space and image. The practice led research reflected on creation of artworks from three perspectives – material, immaterial and hybrid – and in doing so, developed a new methodological structure that extends conventional forms of triangulation. This study explored how physical and digital elements each sought hierarchical presence, yet simultaneously coexisted, thereby extending the visual and conceptual potential of the work. Outcomes demonstrated how utilising and recording transitional processes of hybrid imagery achieved a convergence of diverse, experiential forms. "Hybrid authority" – an authentic convergence of disparate elements – was articulated in the creation and public sharing of processual works and the creation of an innovative framework for hybrid art practice.