Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK.

Prevalence of depressive symptoms as elicited by Patient Health Questionnaire (PHQ-9) among medical trainees in Oman

Background Despite the increasing recognition that medical training tends to coincide with markedly high levels of stress and distress, there is a dearth of validated measures that are capable of gauging the prevalence of depressive symptoms among medical residents in the Arab/Islamic part of the world. Objective The aim of the present study is two-fold. First is to examine the diagnostic validity of the Patient Health Questionnaire (PHQ-9) using an Omani medical resident population in order to establish a cut-off point. Second is to compare gender, age, and residency level among Omani Medical residents who report current depressive symptomatology versus those who report as non-depressed according to PHQ-9 cut-off threshold. Results A total of 132 residents (42 males and 90 females) consented to participate in this study. The cut-off score of 12 on the PHQ-9 revealed a sensitivity of 80.6% and a specificity of 94.0%. The rate of depression, as elicited by PHQ-9, was 11.4%. The role of gender, age, and residency level was not significant in endorsing depression. Conclusion This study indicated that PHQ-9 is a reliable measure among this cross-cultural population. More studies employing robust methodology are needed to confirm this finding.

Self in the City : Young Adult Fiction about New York City after 9/11

This chapter discusses fictional texts set in New York City soon after Septem- ber 11, 2001 (9/11), or whose characters are affected by the attacks on the World Trade Center. Whereas these texts may not have been directly marketed at young adults, they all address ‘youth issues’. Each of the books discussed here contain or are focalized through the eyes of adolescent protagonists. They are all coming-of-age narratives in that the crises within them are usually a result of a catastrophe, taking the characters on journeys of self-discovery, which, once fulfilled, lead them back home.1 As Jerry Griswold (1992) has suggested, coming-of-age stories are especially well suited to the American psyche, and are already familiar to readers of literature based in New York City (the most familiar work being J.D. Salinger’s The Catcher in the Rye). As with other clas- sic American young adult (YA) literature, the journey and homecoming com- monly associated with coming-of-age are often employed in fiction about 9/11. With the key elements of loss and suffering, self-awareness, introspection, and growth, the coming-of-age novel also fulfils agendas common to both litera- ture and politics: the literary journey becomes the nation’s journey.

Rediscovering the double Friedel-Crafts acylation : an expedient entry to phenanthrene-9,10-diones

The double Friedel–Crafts acylation of readily accessible biaryls with oxalyl chloride delivers the respective phenanthrene-9,10-diones, providing an alternative to the traditional methods, which require harsh oxidizing conditions and multistep sequences. This simple method allows the synthesis of various symmetrical and non-symmetrical targets, and is even effective for the synthesis of the parent ring system from (unactivated) biphenyl.

Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage

A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial-mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0-3, 6-9 or 10-13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.

Changes in ocular biometrics and refraction during near work in downward gaze over time

PURPOSE To investigate changes in the characteristics of the corneal optics, total optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 min. METHODS Ten emmetropes (mean - 0.14 ± 0.24 DS) and 10 myopes (mean - 2.26 ± 1.42 DS) aged from 18 to 30 years were recruited. To measure ocular biometrics and corneal topography in downward gaze, an optical biometer (Lenstar LS900) and a rotating Scheimpflug camera (Pentacam HR) were inclined on a custom built, height and tilt adjustable table. The total optics of the eye were measured in downward gaze with binocular fixation using a modified Shack-Hartmann wavefront sensor. Initially, subjects performed a distance viewing task at primary gaze for 10 min to provide a "wash-out" period for prior visual tasks. A distance task (watching video at 6 m) in downward gaze (25°) and a near task (watching video on a portable LCD screen with 2.5 D accommodation demand) in primary gaze and 25°downward gaze were then carried out, each for 10 min in a randomized order. During measurements, in dichoptic view, a Maltese cross was fixated with the right (untested) eye and the instrument’s fixation target was fixated with the subject’s tested left eye. Immediately after (0 min), 5 and 10 min from the commencement of each trial, measurements of ocular parameters were acquired in downward gaze. RESULTS Axial length exhibited a significant increase with downward gaze and accommodation over time (p<0.05). The greatest axial elongation was observed in downward gaze with 2.5 D accommodation after 10 min (mean change from baseline 23±3 µm). Downward gaze also caused greater changes in anterior chamber depth (ACD) and lens thickness (LT) with accommodation (ACD mean change -163±12µm at 10 min; LT mean change 173±17 µm at 10 min) compared to primary gaze with accommodation (ACD mean change -138±12µm at 10 min; LT mean change 131±15 µm at 10 min). Both corneal power and total ocular power changed by a small but significant amount with downward gaze (p<0.05), resulting in a myopic shift (~0.10 D) in the spherical power of the eye compared with primary gaze. CONCLUSION The axial length, anterior biometrics and ocular refraction change significantly with accommodation in downward gaze as a function of time. These findings provide new insights into the optical and bio-mechanical changes of the eye during typical near tasks.

MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial-mesenchymal transition traits

We have investigated the gelatinase profiles and invasiveness of clonal tumour sublines derived from a spontaneously arising mammary tumour in a Balb/cfC3H mouse. The 67NR, 66c14 and 4T1.2 sublines have low, intermediate and high metastatic potential respectively. In Boyden chamber studies, Matrigel invasion was seen to be progressively higher in the more metastatic lines 4T1.2>66c14>67NR, consistent with MMP-2 activation potential, MMP-9 secretion, and migration over either type I or IV collagen, which were low in both 67NR and 66c14 cells compared to 4T1.2 cells. These attributes are consistent with those seen in human breast cancer cell lines which appear to have undergone an epithelial-mesenchymal transition (EMT) as indicated by vimentin expression. We were, however, surprised to find vimentin expression, MT1-MMP expression and stellate Matrigel outgrowth in the non-invasive, non-metastatic 67NR cells, indicating that they had undergone an EMT despite not being invasive. We conclude that the EMT is manifested to differing degrees in these three clonal cell lines, and that the 67NR cells have either undergone a partial EMT or have since lost certain important attributes of the EMT-derived phenotype. This model should prove useful in further characterizing the regulation of MT1-MMP mediated MMP-2 activation and delineating the EMT in breast cancer progression.

Steady state genuine multipartite entanglement in harmonic oscillator ensembles with a common environment

Steady state entanglement in ensembles of harmonic oscillators with a common squeezed reservoir is studied. Under certain conditions the ensemble features genuine multipartite entanglement in the steady state. Several analytic results regarding the bipartite and multipartite entanglement properties of the system are derived. We also discuss a possible experimental implementation which may exhibit steady state genuine multipartite entanglement.

A study of the effects metal residues in poly(9,9-dioctylfluorene) have on field-effect transistor device characteristics

The amount of metal residues from organometallic reagents used in preparation of poly(9,9-dioctylfluorene) by palladium catalysed Suzuki and nickel-induced Yamamoto polycondensations have been determined, and their effect upon the behaviour of the polymer in field-effect transistors (FETs) has been measured. The metal levels from material polymerised by Suzuki method were found to be much higher than from that made by the Yamamoto procedure. Simple treatment of the polymers with suitable metal trapping reagents lowered the metal levels significantly, with EDTA giving best results for nickel and triphenylphosphine for palladium. Comparison of the behaviour of FETs using polyfluorenes with varying levels of metal contamination, showed that the metal residues have little effect upon the mobility values, but often affect the degree of hysteresis, possibly acting as charge traps. Satisfactory device performances were obtained from polymer with palladium levels of 2000 μg/g suggesting that complete removal of metal residues may not be necessary for satisfactory device performance.

Auditor independence : an analysis of the adequacy of selected provisions in CLERP 9

Worldwide corporate collapses in the past have highlighted various weaknesses in corporate governance, which included auditor independence. This thesis advocates the use of private interest theory as a framework to evaluate proposals for law reform related to the independence of external company auditors. This study argues that the current regulation of auditor independence falls short of the 'ideal independence' required by the general public. This is because the regulation was developed, in some instances, to serve the private interests of powerful lobby groups rather than the public interest. This research concludes that there is a case for reform of the existing requirements in the Corporations Act 2001 (Cth) in respect of auditor independence.

Effect of diabetes on amplitude of accommodation

Purpose: To determine the effect of Type 1 diabetes (DM1) on amplitude of accommodation. Method: There were 43 participants (33 ± 8 years) with DM1 and 32 (34 ± 8 years) age-balanced controls. Amplitude was measured objectively with a COAS wavefront aberrometer and subjectively with a Badal hand optometer. Results: Across both groups, objective amplitude was less than subjective amplitude by 1.4 ± 1.2 D. People with diabetes had lower objective (2.7±1.6 D) and subjective (4.0±1.7 D) amplitudes than people without diabetes (objective 4.1±2.1 D, subjective 5.6±2.1 D). For the DM1 group, the objective and subjective multivariate linear regressions were 7.1 – 0.097Age – 0.076DiabDur (R2 0.51) and 9.1 –0.103Age – 0.106DiabDur (R2 0.63), respectively. Conclusion: Objective and subjective techniques showed lowered amplitude of accommodation in DM1 participants compared with age-matched controls. Loss was affected strongly by duration of diabetes. People with diabetes will experience presbyopia earlier in life than people without diabetes.

Optics of the human eye in diabetes

This study compared optics of eyes in people with diabetes with those age-balanced controls. Relative to the control group, the diabetes group demonstrated greater lens thickness, more curved lens shapes, smaller lens diameters, higher light scatter, greater lens yellowing, and poorer focusing ability. While the optics of the people with diabetes made them appear as older eyes than those of people of the same age without diabetes, the differences did not increase significantly with age. It was concluded that age-related changes in eyes of people with diabetes need not be accelerated if the diabetes is well controlled.

A multiple case study of NAPLAN numeracy testing of Year 9 students in three Queensland secondary schools

This thesis reports on a multiple case study of the actions of three Queensland secondary schools in the context of Year 9 NAPLAN numeracy testing, focusing on their administrative practices, curriculum, pedagogy and assessment. It was established that schools have found it both challenging and costly to operate in an environment of educational reform generally, and NAPLAN testing in particular. The lack of a common understanding of numeracy and the substantial demands of implementing the Australian Curriculum have impacted on schools' ability to prepare students appropriately for NAPLAN numeracy tests. It was concluded that there is scope for schools to improve their approaches to NAPLAN numeracy testing in a way that maximises learning as well as test outcomes.