The role of insulin in advanced prostate cancer

Advanced prostate cancer is a common and generally incurable disease. Androgen deprivation therapy is used to treat advanced prostate cancer with good benefits to quality of life and regression of disease. Prostate cancer invariably progresses however despite ongoing treatment, to a castrate resistant state. Androgen deprivation is associated with a form of metabolic syndrome, which includes insulin resistance and hyperinsulinaemia. The mitogenic and anti-apoptotic properties of insulin acting through the insulin and hybrid insulin/IGF-1 receptors seem to have positive effects on prostate tumour growth. This pilot study was designed to assess any correlation between elevated insulin levels and progression to castrate resistant prostate cancer. Methods: 36 men receiving ADT for advanced prostate cancer were recruited, at various stages of their treatment, along with 47 controls, men with localised prostate cancer pre-treatment. Serum measurements of C-peptide (used as a surrogate marker for insulin production) were performed and compared between groups. Correlation between serum C-peptide level and time to progression to castrate resistant disease was assessed. Results: There was a significant elevation of C-peptide levels in the ADT group (mean = 1639pmol/L)) compared to the control group (mean = 1169pmol/L), with a p-value of 0.025. In 17 men with good initial response to androgen deprivation, a small negative trend towards earlier progression to castrate resistance with increasing C-peptide level was seen in the ADT group (r = -0.050), however this did not reach statistical significance (p>0.1). Conclusions: This pilot study confirms an increase in serum C-peptide levels in men receiving ADT for advance prostate cancer. A non-significant, but negative trend towards earlier progression to castrate resistance with increasing C-peptide suggests the need for a formal prospective study assessing this hypothesis.

Embedded criminology and knowledges of resistance

This chapter explores the changing intellectual landscapes and market-led research within academic institutions as the rise of 'embedded criminology' and argues for knowledges of resistance.

Do the myths still exist? Revisiting people’s negative beliefs about organ donation upon death

The prevalence of myths preventing people partial to donation in Australia from consenting is unknown. Respondents (N = 468: 381 donors, 26 non-donors, 61 undecided) were surveyed about their (negative) donation beliefs. Approximately 30% of donors were neutral or supported negative beliefs about organ allocation, especially donation to undesirable organ recipients and a black market organ trade. Confusion about brain death, lack of family and religious support, and discomfort with donation were negative beliefs endorsed by some respondents irrespective of donor preference. Proportionally, donors had greater trust in hospitals/doctors than other groups. Some myths still exist but may vary with donation preference.

Negative space and positive environment : mapping opportunities for urban resilience

Cities have long held a fascination for people – as they grow and develop, there is a desire to know and understand the intricate interplay of elements that makes cities ‘live’. In part, this is a need for even greater efficiency in urban centres, yet the underlying quest is for a sustainable urban form. In order to make sense of the complex entities that we recognise cities to be, they have been compared to buildings, organisms and more recently machines. However the search for better and more elegant urban centres is hardly new, healthier and more efficient settlements were the aim of Modernism’s rational sub-division of functions, which has been translated into horizontal distribution through zoning, or vertical organisation thought highrise developments. However both of these approaches have been found to be unsustainable, as too many resources are required to maintain this kind or urbanisation and social consequences of either horizontal or vertical isolation must also be considered. From being absolute consumers of resources, of energy and of technology, cities need to change, to become sustainable in order to be more resilient and more efficient in supporting culture, society as well as economy. Our urban centres need to be re-imagined, re-conceptualised and re-defined, to match our changing society. One approach is to re-examine the compartmentalised, mono-functional approach of urban Modernism and to begin to investigate cities like ecologies, where every element supports and incorporates another, fulfilling more than just one function. This manner of seeing the city suggests a framework to guide the re-mixing of urban settlements. Beginning to understand the relationships between supporting elements and the nature of the connecting ‘web’ offers an invitation to investigate the often ignored, remnant spaces of cities. This ‘negative space’ is the residual from which space and place are carved out in the Contemporary city, providing the link between elements of urban settlement. Like all successful ecosystems, cities need to evolve and change over time in order to effectively respond to different lifestyles, development in culture and society as well as to meet environmental challenges. This paper seeks to investigate the role that negative space could have in the reorganisation of the re-mixed city. The space ‘in-between’ is analysed as an opportunity for infill development or re-development which provides to the urban settlement the variety that is a pre-requisite for ecosystem resilience. An analysis of the urban form is suggested as an empirical tool to map the opportunities already present in the urban environment and negative space is evaluated as a key element in achieving a positive development able to distribute diverse environmental and social facilities in the city.

Text mining in negative relevance feedback

It is a big challenge to clearly identify the boundary between positive and negative streams. Several attempts have used negative feedback to solve this challenge; however, there are two issues for using negative relevance feedback to improve the effectiveness of information filtering. The first one is how to select constructive negative samples in order to reduce the space of negative documents. The second issue is how to decide noisy extracted features that should be updated based on the selected negative samples. This paper proposes a pattern mining based approach to select some offenders from the negative documents, where an offender can be used to reduce the side effects of noisy features. It also classifies extracted features (i.e., terms) into three categories: positive specific terms, general terms, and negative specific terms. In this way, multiple revising strategies can be used to update extracted features. An iterative learning algorithm is also proposed to implement this approach on RCV1, and substantial experiments show that the proposed approach achieves encouraging performance.

Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from freeDNAwere present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.

Negative change and job outcomes : the impact of subjective fit in public sector health care organization

There is an ongoing level of organizational-wide change (such as empowerment and downsizing) occurring within the Australian health care sector. However, there is a paucity of empirical evidence on how public and nonprofit sector nurses cope with these organizational-wide change initiatives and their consequences on individual and work outcomes. This will be the primary aim of the current paper. To this end, a path model is developed base on an integration of existing theoretical perspectives on occupational stress, change management, and person-organizational fit. Data were collected from 252 public and not-for-profit sector nurses. The path analysis suggests that public and nonprofit nurses experience positive and negative change initiatives. Negative change initiatives resulted in an increase in the level of administrative-related stressors. Nurses with more congruent values report less experience with administrative stressors. As nurses experienced more administrative stressors, they tend to report more job dissatisfaction. Nurses whose values were more congruent during organizational change reported higher level of psychological wellbeing. Nurses who were had higher level of psychological wellbeing were found to have higher job satisfaction, which subsequently led to a higher level of organizational commitment.

Early inflammatory and myogenic responses to resistance exercise in the elderly

Introduction and Methods: This study compared changes in myokine and myogenic genes following resistance exercise (3 sets of 12 repetitions of maximal unilateral knee extension) in 20 elderly men (67.8 ± 1.0 years) and 15 elderly women (67.2 ± 1.5 years). Results: Monocyte chemotactic protein (MCP)-1, macrophage inhibitory protein (MIP)-1β, interleukin (IL)-6 and MyoD mRNA increased significantly (P < 0.05), whereas myogenin and myostatin mRNA decreased significantly after exercise in both groups. Macrophage-1 (Mac-1) and MCP-3 mRNA did not change significantly after exercise in either group. MIP-1β, Mac-1 and myostatin mRNA were significantly higher before and after exercise in men compared with women. In contrast, MCP-3 and myogenin mRNA were significantly higher before and after exercise in the women compared with the men. Conclusions: In elderly individuals, gender influences the mRNA expression of certain myokines and growth factors, both at rest and after resistance exercise. These differences may influence muscle regeneration following muscle injury

Wolbachia-mediated resistance to dengue virus infection and death at the cellular level

Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown.

Inflammatory cytokine responses to progressive resistance training and supplementation with fortified milk in men aged 50+ years : an 18-month randomized controlled trial

We examined the effects of progressive resistance training (PRT) and supplementation with calcium-vitamin D(3) fortified milk on markers of systemic inflammation, and the relationship between inflammation and changes in muscle mass, size and strength. Healthy men aged 50-79 years (n = 180) participated in this 18-month randomized controlled trial that comprised a factorial 2 x 2 design. Participants were randomized to (1) PRT + fortified milk supplement, (2) PRT, (3) fortified milk supplement, or (4) a control group. Participants assigned to PRT trained 3 days per week, while those in the supplement groups consumed 400 ml day(-1) of milk containing 1,000 mg calcium plus 800 IU vitamin D(3). We collected venous blood samples at baseline, 12 and 18 months to measure the serum concentrations of IL-6, TNF-alpha and hs-CRP. There were no exercise x supplement interactions, but serum IL-6 was 29% lower (95% CI, -62, 0) in the PRT group compared with the control group after 12 months. Conversely, IL-6 was 31% higher (95% CI, -2, 65) in the supplement group compared with the non-supplemented groups after 12 and 18 months. These between-group differences did not persist after adjusting for changes in fat mass. In the PRT group, mid-tibia muscle cross-sectional area increased less in men with higher pre-training inflammation compared with those men with lower inflammation (net difference similar to 2.5%, p < 0.05). In conclusion, serum IL-6 concentration decreased following PRT, whereas it increased after supplementation with fortified milk concomitant with changes in fat mass. Furthermore, low-grade inflammation at baseline restricted muscle hypertrophy following PRT.