Identification of bifunctional GA and AG intrastrand crosslinks formed between cisplatin and DNA

A combination of enzymatic digestion and electrospray ionisation mass spectrometry (ESI-MS) was used to characterise bifunctional adducts in which cisplatin is bound to GA base sequences in 8mer and 16mer oligonucleotides that do not contain other, higher affinity binding sites. The extent of formation of bifunctional adducts with GA base sequences was significant, but less than that seen with similar oligonucleotides containing either AG or GG sequences.

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.

The effect of intraoperative force on scoliosis correction at the apex : a biomechanical investigation

Adolescent idiopathic scoliosis (AIS) is a complex 3D deformity of the spine, which may require surgical correction in severe cases. Computer models of the spine provide a potentially powerful tool to virtually ‘test’ various surgical scenarios prior to surgery. Using patient-specific computer models of seven AIS patients who had undergone a single rod anterior procedure, we have recently found that the majority of the deformity correction occurs at the apical joint or the joint immediately cephalic to the apex. In the current paper, we investigate the biomechanics of the apical joint for these patients using clinically measured intra-operative compressive forces applied during implant placement. The aim of this study is to determine a relationship between the compressive joint force applied intra-operatively and the achievable deformity correction at the apical joint.

A computer model to simulate scoliosis surgery

Use of patient-specific computer models as a pre-operative planning tool permits predictions of the likely deformity correction and allows a more detailed investigation of the biomechanical influence of different surgical procedures on the scoliotic spinal anatomy. In this paper, patient-specific computer models are used of adolescent idiopathic scoliosis patients who underwent a single rod anterior procedure at the Mater Children’s Hospital in Brisbane, to predict deformity correction and to investigate the change in biomechanics of the scoliotic spine due to surgical compressive forces applied during implant placement.

Is the iPhone a useful clinical tool to monitor spinal deformity patients?

The progression of spinal deformity is traditionally monitored on hard copy radiographs using the Cobb method with a protractor and pencil. The rotation of the spine and ribcage (rib hump) in scoliosis is measured with a hand-held inclinometer/Scoliometer. The iPhone and other smart phones, can accurately sense inclination, and can therefore be used to measure Cobb angles and rib hump angulation. The purpose of this study was to quantify the performance of the iPhone compared to the standard protractor (Cobb angles) and the Scoliometer (rib hump).

Factors influencing health behaviours of younger women after menopause-inducing cancer treatment

Objective To investigate the health promotion and risk reduction behaviors of younger women previously treated for cancer. Design and Sample Guided by the Precede-Proceed framework, a mixed-method descriptive investigation of the health behaviors of younger women with cancer treatment-induced menopause in one health jurisdiction in Australia was undertaken. Measures This article reports the results of the qualitative interview component of the study. Results Of the 85 women who responded to surveys that quantified their health behaviors, 22 consented to interviews that explored how and why these behaviors might occur. Conclusions Several predisposing, enabling and reinforcing factors that influenced participants will or ability to engage with health-promoting behaviors after cancer treatment were identified in the interviews. These include entrenched precancer diagnosis health behaviors, the disabilities resulting from cancer treatments, perceptions of risk, focused intervention by health professionals and the nature of participants social support. The results indicate a need for flexibility when planning public health initiatives to prepare this cohort for a healthy life after cancer, which accounts for their developmental, knowledge and posttreatment needs.

Bicyclists overestimate their own night-time conspicuity and underestimate the benefits of retroreflective markers on the moveable joints

Conspicuity limitations make bicycling at night dangerous. This experiment quantified bicyclists’ estimates of the distance at which approaching drivers would first recognize them. Twenty five participants (including 13 bicyclists who rode at least once per week, and 12 who rode once per month or less) cycled in place on a closed-road circuit at night-time and indicated when they were confident that an approaching driver would first recognize that a bicyclist was present. Participants wore black clothing alone or together with a fluorescent bicycling vest, a fluorescent bicycling vest with additional retroreflective tape, or the fluorescent retroreflective vest plus ankle and knee reflectors in a modified ‘biomotion’ configuration. The bicycle had a light mounted on the handlebars which was either static, flashing or off. Participants judged that black clothing made them least visible, retroreflective strips on the legs in addition to a retroreflective vest made them most visible and that adding retroreflective materials to a fluorescent vest provides no conspicuity benefits. Flashing bicycle lights were associated with higher conspicuity than static lights. Additionally, occasional bicyclists judged themselves to be more visible than did frequent bicyclists. Overall, bicyclists overestimated their conspicuity compared to previously collected recognition distances and underestimated the conspicuity benefits of retroreflective markings on their ankles and knees. Participants mistakenly judged that a fluorescent vest that did not include retroreflective material would enhance their night-time conspicuity. These findings suggest that bicyclists have dangerous misconceptions concerning the magnitude of the night-time conspicuity problem and the potential value of conspicuity treatments.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Barriers to formal IT Governance practice - insights from a qualitative study

IT Governance (ITG) continues to be a top priority for organizations, public and non-public. While the level of awareness towards ITG is evident, it is hardly manifested in practice. The purpose of this study is to elicit factors that act as barriers to the adoption of formal ITG practice. This qualitative study consists of 9 semi-structured interviews with the key person in charge of ITG adoption and practice within their respective organizations. The interviews were analyzed using thematic content analysis, guided by themes previously obtained from the literature and from an earlier pilot study. Findings obtained supported previous findings and also reveal new factors noticeably absent from the ITG literature. The findings will provide useful input towards the development of a causal model on barriers to formal ITG practice

A proposed Australian industrial control system security curriculum

The security of industrial control systems in critical infrastructure is a concern for the Australian government and other nations. There is a need to provide local Australian training and education for both control system engineers and information technology professionals. This paper proposes a postgraduate curriculum of four courses to provide knowledge and skills to protect critical infrastructure industrial control systems. Our curriculum is unique in that it provides security awareness but also the advanced skills required for security specialists in this area. We are aware that in the Australian context there is a cultural gap between the thinking of control system engineers who are responsible for maintaining and designing critical infrastructure and information technology professionals who are responsible for protecting these systems from cyber attacks. Our curriculum aims to bridge this gap by providing theoretical and practical exercises that will raise the awareness and preparedness of both groups of professionals.

Can testosterone replacement decrease the memory problem of old age?

The world is rapidly ageing. It is against this backdrop that there are increasing incidences of dementia reported worldwide, with Alzheimer's disease (AD) being the most common form of dementia in the elderly. It is estimated that AD affects almost 4 million people in the US, and costs the US economy more than 65 million dollars annually. There is currently no cure for AD but various therapeutic agents have been employed in attempting to slow down the progression of the illness, one of which is oestrogen. Over the last decades, scientists have focused mainly on the roles of oestrogen in the prevention and treatment of AD. Newer evidences suggested that testosterone might also be involved in the pathogenesis of AD. Although the exact mechanisms on how androgen might affect AD are still largely unknown, it is known that testosterone can act directly via androgen receptor-dependent mechanisms or indirectly by converting to oestrogen to exert this effect. Clinical trials need to be conducted to ascertain the putative role of androgen replacement in Alzheimer's disease.

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction. We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini- open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. Methods. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion was assessed at six months post-surgery. Results. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL- based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL- based scaffold group in all loading directions in comparison to the other two groups. Conclusions. The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.

The effect of testing protocol on immature bovine thoracic spine segment stiffness

Introduction. In vitro spine biomechanical testing has been central to many advances in understanding the physiology and pathology of the human spine. Owing to the difficulty in obtaining sufficient numbers of human samples to conduct these studies, animal spines have been accepted as a substitute model. However, it is difficult to compare results from different studies, as they use different preparation, testing and data collection methods. The aim of this study was to identify the effect of repeated cyclic loading on bovine spine segment stiffness. It also aimed to quantify the effect of multiple freeze-thaw sequences, as many tests would be difficult to complete in a single session [1-3]. Materials and Methods. Thoracic spines from 6-8 week old calves were used. Each spine was dissected and divided into motion segments including levels T4-T11 (n=28). These were divided into two equal groups. Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37 degrees C and 100% humidity, using moment control to a maximum plus/minus 1.75 Nm with a loading rate of 0.3 Nm per second. Group (A) were tested with continuous repeated cyclic loading for 500 cycles with data recorded at cycles 3, 5, 10, 25, 100, 200, 300, 400 and 500. Group (B) were tested with 10 load cycles after each of 5 freeze thaw sequences. Data was collected from the tenth load cycle after each sequence. Statistical analysis of the data was performed using paired samples t-tests, ANOVA and generalized estimating equations. Results. The data were confirmed as having a normal distribution. 1. There were significant reductions in mean stiffness in flexion/extension (-20%; P=0.001) and lateral bending (-17%; P=0.009) over the 500 load cycles. However, there was no statistically significant change in axial rotation (P=0.152) 2. There was no statistically significant difference between mean stiffness over the five freeze-thaw sequences in flexion/extension (p=0.879) and axial rotation (p=0.07). However, there was a significant reduction in stiffness in lateral bending (-26%; p=0.007) Conclusion. Biomechanical testing of immature bovine spine motion segments requires careful interpretation. The effect of the number of load cycles as well as the number of freeze-thaw cycles on the stiffness of the motion segments depends on the axis of main movement.