Tissue-engineered 3D tumor angiogenesis models : potential technologies for anti-cancer drug discovery

Angiogenesis is indispensable for solid tumor expansion, and thus it has become a major target of cancer research and anti-cancer therapies. Deciphering the arcane actions of various cell populations during tumor angiogenesis requires sophisticated research models, which could capture the dynamics and complexity of the process. There is a continuous need for improvement of existing research models, which engages interdisciplinary approaches of tissue engineering with life sciences. Tireless efforts to develop a new model to study tumor angiogenesis result in innovative solutions, which bring us one step closer to decipher the dubious nature of cancer. This review aims to overview the recent developments, current limitations and future challenges in three-dimensional tissue-engineered models for the study of tumor angiogenesis and for the purpose of elucidating novel targets aimed at anti-cancer drug discovery.

Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes : Development of a potential measure of diabetic peripheral neuropathy

Purpose To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes. Methods A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) and were quantified using a fully-automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time. Results At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared to controls (P<0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, -0.9 nerve/mm2, P=0.01) in the neuropathy group compared to controls, which was associated with age (β=-0.06, P=0.04) and duration of diabetes (β=-0.08, P=0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (rs, 0.38 and 0.40, P<0.05). Conclusion This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of DPN.

Perceived needs for supported self-management of type 2 diabetes : a qualitative investigation of the potential for a web-based intervention

The estimated one million Australians with type 2 diabetes face significant risks of morbidity and premature mortality. Inadequate diabetes self-management is associated with poor glycaemic control, which is further impaired by comorbid dysphoria. Regular access to ongoing self-management and psychological support is limited, especially in rural and regional locations. Web-based interventions can provide complementary support to patients’ usual care. Semi-structured interviews were undertaken with two samples that comprised (a) 13 people with type 2 diabetes and (b) 12 general practitioners (GPs). Interviews explored enablers and barriers to self-care, emotional challenges, needs for support, and potential web-based programme components. Patients were asked about the potential utility of a web-based support programme, and GPs were asked about likely circumstances of patient referral to it. Thematic analysis was used to summarise responses. Most perceived facilitators and barriers to self-management were similar across the groups. Both groups highlighted the centrality of dietary self-management, valued shared decision-making with health professionals, and endorsed the idea of web-based support. Some emotional issues commonly identified by patients varied to those perceived by GPs, resulting in different attributions for impaired self-care. A web-based programme that supported self-management and psychological/emotional needs appears likely to hold promise in yielding high acceptability and perceived utility.

Causal factors of hot air ballooning incidents : identification, frequency, and potential impact

Background: Hot air ballooning incidents are relatively rare, however, when they do occur they are likely to result in a fatality or serious injury. Human error is commonly attributed as the cause of hot air ballooning incidents; however, error in itself is not an explanation for safety failures. This research aims to identify, and establish the relative importance of factors contributing towards hot air ballooning incidents. Methods: Twenty-two Australian Ballooning Federation (ABF) incident reports were thematically coded using a bottom up approach to identify causal factors. Subsequently, 69 balloonists (mean 19.51 years’ experience) participated in a survey to identify additional causal factors and rate (out of seven) the perceived frequency and potential impact to ballooning operations of each of the previously identified causal factors. Perceived associated risk was calculated by multiplying mean perceived frequency and impact ratings. Results: Incident report coding identified 54 causal factors within nine higher level areas: Attributes, Crew resource management, Equipment, Errors, Instructors, Organisational, Physical Environment, Regulatory body and Violations. Overall, ‘weather’, ‘inexperience’ and ‘poor/inappropriate decisions’ were rated as having greatest perceived associated risk. Discussion: Although errors were nominated as a prominent cause of hot air ballooning incidents, physical environment and personal attributes are also particularly important for safe hot air ballooning operations. In identifying a range of causal factors the areas of weakness surrounding ballooning operations have been defined; it is hoped that targeted safety and training strategies can now be put into place removing these contributing factors and reducing the chance of pilot error.

Board monitoring and the balanced scorecard in nonprofits : challenges in realising potential

Directors of nonprofits in most countries have legal responsibility for monitoring organisational performance (Brody 2010), although there is typically little guidance on how this should occur. The balanced scorecard (BSC) (Kaplan & Norton, 1996, 2001) potentially provides boards with a monitoring tool (Kaplan $ Norton, 2006; Lorsch, 2002). The BSC is intended to help integrate performance measurement, performance management and strategy implmentation (Kaplan 2009). The scorecards is balanced in that it should incorporate both financial and non-financial measures, external and internal perspectives, short and long-term objectives and both lagging and leading indicators. It is a relatively simple tool, but with potentially profound implications for directing board attention and sbusequent action (Ocasio, 1997; Salterio, 2012).

Translocation of bats as a conservation strategy : previous attempts and potential problems

Translocation is an increasingly popular conservation tool from which a wide range of taxa have benefited. However, to our knowledge, bats have not been translocated successfully. Bats differ behaviourally, morphologically and physiologically from the taxa for which translocation the- ory has been developed, so existing guidelines may not be directly transferable. We review previous translocations of bats and discuss characteristics of bats that may require special consideration dur- ing translocation. Their vagility and homing ability, coloniality, roost requirements, potential ability to transmit diseases, susceptibility to anthropomorphic impacts, and cryptic nature have implications for establishing populations, effects of these populations on the release site, and ability to monitor translocation success following release. We hope that our discussion of potential problems will be able to supplement the existing, more generic guidelines to provide a starting point for the planning of bat translocations.

The potential availability of roosting sites for lesser short-tailed bats (Mystacina tuberculata) on Kapiti Island, New Zealand: Implications for a translocation

Lesser short-tailed bats (Mystacina tuberculata) have recently been translocated to Kapiti Island in an attempt to form a new population of this threatened species. However, the island's vegetation is regenerating, and there was doubt that the forests provided enough large trees with cavities for bats to roost in. This study measured the availability of tree-trunk cavities of the right size for potential roost sites on Kapiti Island, and assessed if habitat restoration would be required to increase the translocation's chance of success. First, trees with cavities accessible to us were sampled in six of Kapiti Island's forest types. Size variables known to affect roost site selection by lesser short-tailed bats at the tree and cavity level were measured. Trees were classified as containing cavities that could potentially provide suitable roosts if their values for all variables measured fell within the range of roosts used by lesser short-tailed bats in natural populations. Roosts were classified as suitably sized for solitary bats or for colonies, using measurements from both types of roosts in natural populations. Second, the density of these potential roost cavities was calculated. Cavities of a size potentially suitable for colonies were found in four of the six forest types at densities ranging from 3.2 +/- 3.2 SE to 52.4 +/- 14.0 trees per ha. Density of potential solitary roosts was much higher. Not all potential cavities will be suitable because they may be damp, poorly insulated, or have an unsuitable microclimate. Nevertheless, our estimates indicated that the two most extensive forest types each contained thousands of potential cavities of a size suitable for colonies of lesser short-tailed bats. In addition, there were tens of thousands of cavities large enough to shelter solitary bats. Roost habitat restoration appears unnecessary to assist translocated Mystacina tuberculata on Kapiti Island.

Female greater wax moths reduce sexual display behavior in relation to the potential risk of predation by echolocating bats

Female greater wax moths Galleria mellonella display by wing fanning in response to bursts of ultrasonic calls produced by males. The temporal and spectral characteristics of these calls show some similarities with the echolocation calls of bats that emit frequency-modulated (FM) signals. Female G. mellonella therefore need to distinguish between the attractive signals of male conspecifics, which may lead to mating opportunities, and similar sounds made by predatory bats. We therefore predicted that (1) females would display in response to playbacks of male calls; (2) females would not display in response to playbacks of the calls of echolocating bats (we used the calls of Daubenton's bat Myotis daubentonii as representative of a typical FM echolocating bat); and (3) when presented with male calls and bat calls during the same time block, females would display more when perceived predation risk was lower. We manipulated predation risk in two ways. First, we varied the intensity of bat calls to represent a nearby (high risk) or distant (low risk) bat. Second, we played back calls of bats searching for prey (low risk) and attacking prey (high risk). All predictions were supported, suggesting that female G. mellonella are able to distinguish conspecific male mating calls from bat calls, and that they modify display rate in relation to predation risk. The mechanism (s) by which the moths separate the calls of bat and moth must involve temporal cues. Bat and moth signals differ considerably in duration, and differences in duration could be encoded by the moth's nervous system and used in discrimination.

Review-evaluating the molecular assays for measuring the oxidative potential of particulate matter

Several cell-free assays are currently used to quantify and detect the Reactive Oxygen Species (ROS). All of them have certain limitations, do not provide direct comparison of results and, to date, none of these assays have been acknowledged as the most suitable acellular assay and none has yet been adopted for investigation of potential PM toxicity. These assays include DTT, ascorbic acid, DCFHDA and PFN assays which have been used in measurements of the particles generated from various combustion sources such as diesel engine, wood smoke (or biomass burning) and cigarette smoke, as well as for outdoor measurements. All the probes use different units for expressing redox properties of PM. Also, their reactivity is being triggered by different types of ROS. This limits the direct comparison of the results that are reporting the toxicity of the same aerosol type measured with various probes. This study is evaluating and comparing the various assays in order to develop deeper understanding of their capabilities, selectivity as well as improve understanding of the underlying chemical mechanisms. Keywords: DTT, DCFH-DA, PFN, BPEA-nit, Ascorbic acid, oxidative potential

Is there a potential relationship between prior h amstring strain injury and increased risk for future a nterior cruciate ligament injury?

Hamstring strain injuries (HSIs) are the most prevalent injury in a number of sports, and while anterior cruciate ligament (ACL) injuries are less common, they are far more severe and have long-term implications, such as an increased risk of developing osteoarthritis later in life. Given the high incidence and severity of these injuries, they are key targets of injury preventive programs in elite sport. Evidence has shown that a previous severe knee injury (including ACL injury) increases the risk of HSI; however, whether the functional deficits that occur after HSI result in an increased risk of ACL injury has yet to be considered. In this clinical commentary, we present evidence that suggests that the link between previous HSI and increased risk of ACL injury requires further investigation by drawing parallels between deficits in hamstring function after HSI and in women athletes, who are more prone to ACL injury than men athletes. Comparisons between the neuromuscular function of the male and female hamstring has shown that women display lower hamstring-to-quadriceps strength ratios during isokinetic knee flexion and extension, increased activation of the quadriceps compared with the hamstrings during a stop-jump landing task, a greater time required to reach maximal isokinetic hamstring torque, and lower integrated myoelectrical hamstring activity during a sidestep cutting maneuver. Somewhat similarly, in athletes with a history of HSI, the previously injured limb, compared with the uninjured limb, displays lower eccentric knee flexor strength, a lower hamstrings-to-quadriceps strength ratio, lower voluntary myoelectrical activity during maximal knee flexor eccentric contraction, a lower knee flexor eccentric rate of torque development, and lower voluntary myoelectrical activity during the initial portion of eccentric contraction. Given that the medial and lateral hamstrings have different actions at the knee joint in the coronal plane, which hamstring head is previously injured might also be expected to influence the likelihood of future ACL. Whether the deficits in function after HSI, as seen in laboratory-based studies, translate to deficits in hamstring function during typical injurious tasks for ACL injury has yet to be determined but should be a consideration for future work.

Three-dimensional geological modelling of the Galilee and central Eromanga basins, Australia: New insights into aquifer/aquitard geometry and potential influence of faults on inter-connectivity

Study region The Galilee and Eromanga basins are located in central Queensland, Australia. Both basins are components of the Great Artesian Basin which host some of the most significant groundwater resources in Australia. Study focus This study evaluates the influence of regional faults on groundwater flow in an aquifer/aquitard interbedded succession that form one of the largest Artesian Basins in the world. In order to assess the significance of regional faults as potential barriers or conduits to groundwater flow, vertical displacements of the major aquifers and aquitards were studied at each major fault and the general hydraulic relationship of units that are juxtaposed by the faults were considered. A three-dimensional (3D) geological model of the Galilee and Eromanga basins was developed based on integration of well log data, seismic surfaces, surface geology and elevation data. Geological structures were mapped in detail and major faults were characterised. New hydrological insights for the region Major faults that have been described in previous studies have been confirmed within the 3D geological model domain and a preliminary assessment of their hydraulic significance has been conducted. Previously unknown faults such as the Thomson River Fault (herein named) have also been identified in this study.

Analyzing busway station potential capacity under mixed stopping and non-stopping operation

Busway stations are the interface between passengers and services. The station is crucial to line operation as it is typically the only location where buses can pass each other. Congestion may occur here when buses manoeuvring into and out of the platform lane interfere with bus flow, or when a queue of buses forms upstream of the platform lane blocking the passing lane. Further, some systems include operation where express buses do not observe the station, resulting in a proportion of non-stopping buses. It is important to understand the operation of the station under this type of operation and its effect on busway capacity. This study uses microscopic simulation to treat the busway station operation and to analyse the relationship between station potential capacity where all buses stop, and Mixed Potential Capacity where there is a mixture of stopping and non-stopping buses. First, the micro simulation technique is used to analyze the All Stopping Buses (ASB) scenario and then statistical model is tuned and calibrated for a specified range of controlled scenarios of dwell time characteristics Subsequently, a mathematical model is developed for Mixed Stopping Buses (MSB) Potential Capacity by introducing different proportions of express (or non-stopping) buses. The proposed models for a busway station bus capacity provide a better understanding of operation and are useful to transit agencies in busway planning, design and operation.

Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA

We report that tumor cells devoid of their mitochondrial genome (mtDNA) show delayed tumor growth and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory supercomplexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to re-establish respiration and tumor-initiating efficacy. These results suggest a novel pathophysiological process for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.