Studies of granulosa cell maturation in dominant and subordinate bovine follicles : novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol side-chain cleavage CYP11A1

During growth of antral ovarian follicles granulosa cells first become associated with a novel type of extracellular matrix, focimatrix, and at larger sizes follicles become either subordinate or dominant. To examine this, bovine subordinate (9.0±s.e.m. 0.4 mm; n=16), partially dominant (12.0±0.6 mm; n=18) and fully dominant (15.0±0.4 mm; n=14) follicles were examined by real time RT-PCR analyses of granulosa cells and by immunohistochemistry of focimatrix. Changes in the expression of FSH receptor, LH receptor, cholesterol side-chain cleavage (CYP11A1), 3β-hydroxysteroid dehydrogenase, aromatase (CYP19A1) and inhibin-α and β-B were observed as expected for follicle sizes examined. After adjusting for size differences, only CYP11A1 was significantly different between the groups, and elevated in dominant follicles. Also after adjusting for differences in size there were no significant differences in expression of focimatrix components collagen type IV α-1 (COL4A1), laminin β-2, nidogen 1 (NID1), and perlecan (HSPG2) or the volume density of NID1 and -2 and HSPG2. The volume density of focimatrix components in laminin 111 was significantly elevated in dominant follicles. Adjusting for analysis of more than one follicle per animal and for multiple correlations, CYP11A1 mRNA levels were highly correlated with the focimatrix genes COL4A1, NID1 and -2 and HSPG2. Thus, focimatrix may potentially regulate CYP11A1 expression, and the regulation of both could be important in follicular dominance.

The limits of competition : reasserting a role for consumer protection and fair trading regulation in competitive markets

In this paper we advocate for the continued need for consumer protection and fair trading regulation, even in competitive markets. For the purposes of this paper a ‘competitive market’ is defined as one that has low barriers to entry and exit, with homogenous products and services and numerous suppliers. Whilst competition is an important tool for providing consumer benefits, it will not be sufficient to protect at least some consumers, particularly vulnerable, low income consumers. For this reason, we argue, setting competition as the ‘end goal’ and assuming that consumer protection and consumer benefits will always follow, is a flawed regulatory approach. The ‘end goal’ should surely be consumer protection and fair markets, and a combination of competition law and consumer protection law should be applied in order to achieve those goals.

An experimental research investigation into disused flat rail wagons as bridges with applications for low volume rural roads in Australia

An experimental laboratory investigation was carried out to assess the structural adequacy of a disused PHO Class Flat Bottom Rail Wagon (FRW) for a single lane low volume road bridge application as per the design provisions of the Australian Bridge Design Standard AS 5100(2004). The investigation also encompassed a review into the risk associated with the pre-existing damage in wagons incurred during their service life on rail. The main objective of the laboratory testing of the FRW was to physically measure its performance under the same applied traffic loading it would be required to resist as a road bridge deck. In order to achieve this a full width (5.2m) single lane, single span (approximately 10m), simply supported bridge would be required to be constructed and tested in a structural laboratory. However, the available clear spacing between the columns of the loading portal frame encountered within the laboratory was insufficient to accommodate the 5.2m wide bridge deck excluding clearance normally considered necessary in structural testing. Therefore, only half of the full scale bridge deck (single FRW of width 2.6m) was able to be accommodated and tested; with the continuity of the bridge deck in the lateral direction applied as boundary constraints along the full length of the FRW at six selected locations. This represents a novel approach not yet reported in the literature for bridge deck testing to the best of the knowledge of the author. The test was carried out under two loadings provided in AS 5100 (2004) – one stationary W80 wheel load and the second a moving axle load M1600. As the bridge investigated in the study is a single lane single span low volume road bridge, the risk of pre-existing damage and the expected high cycle fatigue failure potential was assessed as being minimal and hence the bridge deck was not tested structurally for fatigue/ fracture. The high axle load requirements have instead been focussed upon the investigation into the serviceability and ultimate limit state requirements. The testing regime adopted however involved extensive recording of strains and deflections at several critical locations of the FRW. Three locations of W80 point load and two locations of the M1600 Axle load were considered for the serviceability testing; the FRW was also tested under the ultimate load dictated by the M1600. The outcomes of the experimental investigation have demonstrated that the FRW is structurally adequate to resist the prescribed traffic loadings outlaid in AS 5100 (2004). As the loading was directly applied on to the FRW, the laboratory testing is assessed as being significantly conservative. The FRW bridge deck in the field would only resist the load transferred by the running platform, where, depending on the design, composite action might exist – thereby the share of the loading which needs to be resisted by the FRW would be smaller than the system tested in the lab. On this basis, a demonstration bridge is under construction at the time of writing this thesis and future research will involve field testing in order to assess its performance.

p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation

p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected. To study the effect of p53 on melanocyte function and melanomagenesis, we crossed the 'high-p53'Mdm4+/- mouse to the well-established TP-ras0/+ murine melanoma progression model. After treatment with the carcinogen dimethylbenzanthracene (DMBA), TP-ras0/+ mice on the Mdm4+/- background developed fewer tumors with a delay in the age of onset of melanomas compared to TP-ras0/+ mice. Furthermore, we observed a dramatic decrease in tumor growth, lack of metastasis with increased survival of TP-ras0/+: Mdm4+/- mice. Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings. Moreover, global gene expression and network analysis of Nutlin-3-treated primary human melanocytes indicated that cell cycle regulation through the p21WAF1/CIP1 signaling network may be the key anti-melanomagenic activity of p53.

The rules of autogeddon : sex death and law in J G Ballard’s Crash

It was reported that the manuscript of Crash was returned to the publisher with a note reading ‘The author is beyond psychiatric help’. Ballard took the lay diagnosis as proof of complete artistic success. Crash conflates the Freudian tropes of libido and thanatos, overlaying these onto the twentieth century erotic icon, the car. Beyond mere incompetent adolescent copulatory fumblings in the back seat of the parental sedan or the clichéd phallic locomotor of the mid-life Ferrari, Ballard engages the full potentialities of the automobile as the locus and sine qua non of a perverse, though functional erotic. ‘Autoeroticism’ is transformed into automotive, traumatic or surgical paraphilia, driving Helmut Newton’s insipid photo-essays of BDSM and orthopædics into an entirely new dimension, dancing precisely where (but more crucially, because) the ‘body is bruised to pleasure soul’. The serendipity of quotidian accidental collisions is supplanted, in pursuit of the fetishised object, by contrived (though not simulated) recreations of iconographic celebrity deaths. Penetration remains as a guiding trope of sexuality, but it is confounded by a perversity of focus. Such an obsessive pursuit of this autoerotic-as-reality necessitates the rejection of the law of human sexual regulation, requiring the re-interpretation of what constitutes sex itself by looking beyond or through conventional sexuality into Ballard’s paraphiliac and nightmarish consensual Other. This Other allows for (if not demands) the tangled wreckage of a sportscar to function as a transformative sexual agent, creating, of woman, a being of ‘free and perverse sexuality, releasing within its dying chromium and leaking engine-parts, all the deviant possibilities of her sex’.

A mathematical model for genetic regulation of the lactose operon

In this paper we construct a mathematical model for the genetic regulatory network of the lactose operon. This mathematical model contains transcription and translation of the lactose permease (LacY) and a reporter gene GFP. The probability of transcription of LacY is determined by 14 binding states out of all 50 possible binding states of the lactose operon based on the quasi-steady-state assumption for the binding reactions, while we calculate the probability of transcription for the reporter gene GFP based on 5 binding states out of 19 possible binding states because the binding site O2 is missing for this reporter gene. We have tested different mechanisms for the transport of thio-methylgalactoside (TMG) and the effect of different Hill coefficients on the simulated LacY expression levels. Using this mathematical model we have realized one of the experimental results with different LacY concentrations, which are induced by different concentrations of TMG.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients

Background: High-flow nasal cannulae (HFNC) create positive oropharyngeal airway pressure but it is unclear how their use affects lung volume. Electrical impedance tomography (EIT) allows assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (Paw) and end-expiratory lung volume (EELV), and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate (RR), dyspnoea, tidal volume and oxygenation; and the interaction between body mass index (BMI) and EELV. Methods: Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, Paw, PaO2/FiO2 ratio, RR and modified Borg scores were recorded first on low flow oxygen (nasal cannula or Hudson face mask) and then on HFNC. Results: A strong and significant correlation existed between Paw and end-expiratory lung impedance (EELI) (r=0.7, p<0.001). Compared with low flow oxygen, HFNC significantly increased EELI by 25.6% (95% CI 24.3, 26.9) and Paw by 3.0 cmH2O (95% CI 2.4, 3.7). RR reduced by 3.4 breaths per minute (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3) and PaO2/FiO2 ratio improved by 30.6 mmHg (95% CI 17.9, 43.3). HFNC improved subjective dyspnoea scoring (p=0.023). Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (p<0.001). Conclusions: This study suggests that HFNC improve dyspnoea and oxygenation by increasing both EELV and tidal volume, and are most beneficial in patients with higher BMIs.

Planning volunteer responses to low-volume mass gatherings: do event characteristics predict patient workload?

INTRODUCTION: Workforce planning for first aid and medical coverage of mass gatherings is hampered by limited research. In particular, the characteristics and likely presentation patterns of low-volume mass gatherings of between several hundred to several thousand people are poorly described in the existing literature. OBJECTIVES: This study was conducted to: 1. Describe key patient and event characteristics of medical presentations at a series of mass gatherings, including events smaller than those previously described in the literature; 2. Determine whether event type and event size affect the mean number of patients presenting for treatment per event, and specifically, whether the 1:2,000 deployment rule used by St John Ambulance Australia is appropriate; and 3. Identify factors that are predictive of injury at mass gatherings. METHODS: A retrospective, observational, case-series design was used to examine all cases treated by two Divisions of St John Ambulance (Queensland) in the greater metropolitan Brisbane region over a three-year period (01 January 2002-31 December 2004). Data were obtained from routinely collected patient treatment forms completed by St John officers at the time of treatment. Event-related data (e.g., weather, event size) were obtained from event forms designed for this study. Outcome measures include: total and average number of patient presentations for each event; event type; and event size category. Descriptive analyses were conducted using chi-square tests, and mean presentations per event and event type were investigated using Kruskal-Wallis tests. Logistic regression analyses were used to identify variables independently associated with injury presentation (compared with non-injury presentations). RESULTS: Over the three-year study period, St John Ambulance officers treated 705 patients over 156 separate events. The mean number of patients who presented with any medical condition at small events (less than or equal to 2,000 attendees) did not differ significantly from that of large (>2,000 attendees) events (4.44 vs. 4.67, F = 0.72, df = 1, 154, p = 0.79). Logistic regression analyses indicated that presentation with an injury compared with non-injury was independently associated with male gender, winter season, and sporting events, even after adjusting for relevant variables. CONCLUSIONS: In this study of low-volume mass gatherings, a similar number of patients sought medical treatment at small (<2,000 patrons) and large (>2,000 patrons) events. This demonstrates that for low-volume mass gatherings, planning based solely on anticipated event size may be flawed, and could lead to inappropriate levels of first-aid coverage. This study also highlights the importance of considering other factors, such as event type and patient characteristics, when determining appropriate first-aid resourcing for low-volume events. Additionally, identification of factors predictive of injury presentations at mass gatherings has the potential to significantly enhance the ability of event coordinators to plan effective prevention strategies and response capability for these events.

International law and the regulation of violence : shifting perceptions of the legitimacy of the jus ad bellum?

International law’s capacity to influence state behaviour by regulating recourse to violence has been a longstanding source of debate among international lawyers and political scientists. On the one hand, sceptics assert that frequent violations of the prohibition on the use of force have rendered article 2(4) of the UN Charter redundant. They contend that national self-interest, rather than international law, is the key determinant of state behaviour regarding the use of force. On the other hand, defenders of article 2(4) argue first, that most states comply with the Charter framework, and second, that state rhetoric continues to acknowledge the existence of the jus ad bellum. In particular, the fact that violators go to considerable lengths to offer legal or factual justifications for their conduct – typically by relying on the right of self-defence – is advanced as evidence that the prohibition on the use of force retains legitimacy in the eyes of states. This paper identifies two potentially significant features of state practice since 2006 which may signal a shift in states’ perceptions of the normative authority of article 2(4). The first aspect is the recent failure by several states to offer explicit legal justifications for their use or force, or to report action taken in self-defence to the Security Council in accordance with Article 51. Four incidents linked to the global “war on terror” are examined here: Israeli airstrikes in Syria in 2007 and in Sudan in 2009, Turkey’s 2006-2008 incursions into northern Iraq, and Ethiopia’s 2006 intervention in Somalia. The second, more troubling feature is the international community’s apparent lack of concern over the legality of these incidents. Each use of force is difficult to reconcile with the strict requirements of the jus ad bellum; yet none attracted genuine legal scrutiny or debate among other states. While it is too early to conclude that these relatively minor incidents presage long term shifts in state practice, viewed together the two developments identified here suggest a possible downgrading of the role of international law in discussions over the use of force, at least in conflicts linked to the “war on terror”. This, in turn, may represent a declining perception of the normative authority of the jus ad bellum, and a concomitant admission of the limits of international law in regulating violence.

Comparing the medium-term effects of exercise or dietary restriction on appetite regulation and compensatory responses

Previous studies have shown that exercise (Ex) interventions create a stronger coupling between energy intake (EI) and energy expenditure (EE) leading to increased homeostasis of the energy-balance (EB) regulatory system compared to a diet intervention where an un-coupling between EI and EE occurs. The benefits of weight loss from Ex and diet interventions greatly depend on compensatory responses. The present study investigated an 8-week medium-term Ex and diet intervention program (Ex intervention comprised of 500kcal EE five days per week over four weeks at 65-75% maximal heart rate, whereas the diet intervention comprised of a 500kcal decrease in EI five days per week over four weeks) and its effects on compensatory responses and appetite regulation among healthy individuals using a between- and within-subjects design. Effects of an acute dietary manipulation on appetite and compensatory behaviours and whether a diet and/or Ex intervention pre-disposes individuals to disturbances in EB homeostasis were tested. Energy intake at an ad libitum lunch test meal after a breakfast high- and low-energy pre-load (the high energy pre-load contained 556kcal and the low energy pre-load contained 239kcal) were measured at the Baseline (Weeks -4 to 0) and Intervention (Weeks 0 to 4) phases in 13 healthy volunteers (three males and ten females; mean age 35 years [sd + 9] and mean BMI 25 kg/m2 [sd + 3.8]) [participants in each group included Ex=7, diet=5 (one female in the diet group dropped out midway), thus, 12 participants completed the study]. At Weeks -4, 0 and 4, visual analogue scales (VAS) were used to assess hunger and satiety and liking and wanting (L&W) for nutrient and taste preferences using a computer-based system (E-Prime v1.1.4). Ad libitum test meal EI was consistently lower after the HE pre-load compared to the LE pre-load. However, this was not consistent during the diet intervention however. A pre-load x group interaction on ad libitum test meal EI revealed that during the intervention phase the Ex group showed an improved sensitivity to detect the energy content between the two pre-loads and improved compensation for the ad libitum test meal whereas the diet group’s ability to differentiate between the two pre-loads decreased and showed poorer compensation (F[1,10]=2.88, p-value not significant). This study supports previous findings of the effect Ex and diet interventions have on appetite and compensatory responses; Ex increases and diet decreases energy balance sensitivity.