Development of a 3D culture system to study the skeletal metastasis of prostate cancer

In the cancer research field, most in vitro studies still rely on two-dimensional (2D) cultures. However, the trend is rapidly shifting towards using a three-dimensional (3D) culture system. This is because 3D models better recapitulate the microenvironment of cells, and therefore, yield cellular and molecular responses that more accurately describe the pathophysiology of cancer. By adopting technology platforms established by the tissue engineering discipline, it is now possible to grow cancer cells in extracellular matrix (ECM)-like environments and dictate the biophysical and biochemical properties of the matrix. In addition, 3D models can be modified to recapitulate different stages of cancer progression for instance from the initial development of tumor to metastasis. Inevitably, to recapitulate a heterotypic condition, comprising more than one cell type, it requires a more complex 3D model. To date, 3D models that are available for studying the prostate cancer (CaP)-bone interactions are still lacking. Therefore, the aim of this study is to establish a co-culture model that allows investigation of direct and indirect CaP-bone interactions. Prior to that, 3D polyethylene glycol (PEG)-based hydrogel cultures for CaP cells were first developed and growth conditions were optimised. Characterization of the 3D hydrogel cultures show that LNCaP cells form a multicellular mass that resembles avascular tumor. In comparison to 2D cultures, besides the difference in cell morphology, the response of LNCaP cells to the androgen analogue (R1881) stimulation is different compared to the cells in 2D cultures. This discrepancy between 2D and 3D cultures is likely associated with the cell-cell contact, density and ligand-receptor interactions. Following the 3D monoculture study, a 3D direct co-culture model of CaP cells and the human tissue engineered bone (hTEBC) construct was developed. Interactions between the CaP cells and human osteoblasts (hOBs) resulted in elevation of Matrix Metalloproteinase 9 (MMP9) for PC-3 cells and Prostate Specific Antigen (PSA) for LNCaP cells. To further investigate the paracrine interaction of CaP cells and (hOBs), a 3D indirect co-culture model was developed, where LNCaP cells embedded within PEG hydrogels were co-cultured with hTEBC. It was found that the cellular changes observed reflect the early event of CaP colonizing the bone site. In the absence of androgens, interestingly, up-regulation of PSA and other kallikreins is also detected in the co-culture compared to the LNCaP monoculture. This non androgenic stimulation could be triggered by the soluble factors secreted by the hOB such as Interleukin-6. There are also decrease in alkaline phosphatase (ALP) activity and down-regulation of genes of the hOB when co-cultured with LNCaP cells that have not been previously described. These genes include transforming growth factor β1 (TGFβ1), osteocalcin and Vimentin. However, no changes to epithelial markers (e.g E-cadherin, Cytokeratin 8) were observed in both cell types from the co-culture. Some of these intriguing changes observed in the co-cultures that had not been previously described have enriched the basic knowledge of the CaP cell-bone interaction. From this study, we have shown evidence of the feasibility and versatility of our established 3D models. These models can be adapted to test various hypotheses for studies pertaining to underlying mechanisms of bone metastasis and could provide a vehicle for anticancer drug screening purposes in the future.

Clinical performance of a new silicone hydrogel contact lens over 6 months of extended wear

Purpose: Silicone hydrogel contact lenses (CLs) are becoming increasingly popular for daily wear (DW), extended wear (EW) and continuous wear (CW), due to their higher oxygen transmissibility compared to hydrogel CLs. The aim of this study was to investigate the clinical and subjective performance of asmofilcon A (Menicon Co., Ltd), a new surface treated silicone hydrogel CL, during 6-night EW over 6 months (M). Methods: A prospective, randomised, single-masked, monadic study was conducted. N=60 experienced DW soft CL wearers were randomly assigned to wear either asmofilcon A (test: Dk=129, water content (WC)=40%, Nanogloss surface treatment) or senofilcon A (control: Dk=103, WC=38%, PVP internal wetting agent, Vistakon, Johnson & Johnson Vision Care) CLs bilaterally for 6 M on an EW basis. A PHMB-preserved solution (Menicon Co., Ltd) was dispensed for CL care. Evaluations were conducted at CL delivery and after 1 week (W), 4 W, 3 M and 6 M of EW. At each visit, a range of objective and subjective clinical performance measures were assessed. Results: N=50 subjects (83%) successfully completed the study, with the majority of discontinuations due to loss to follow-up (n=3) or moving away/travel (n=5). N=2 subjects experienced adverse events; n=1 unilateral red eye with asmofilcon A and n=1 asymptomatic infiltrate with senofilcon A. There were no significant differences in high or low contrast distance visual acuity (HCDVA or LCDVA) between asmofilcon A and senofilcon A; however, LCDVA decreased significantly over time with both CL types (p<0.05). The two CL types did not vary significantly with respect to any of the objective and subjective measures assessed (p>0.05); CL fitting characteristics and CL surface measurements were very similar and mean bulbar and limbal redness measures were always less than grade 1.0. Superior palpebral conjunctival injection showed a statistically, but not clinically, significant increase over time with both CL types (p<0.05). Corneal staining did not vary significantly between asmofilcon A and senofilcon A (p>0.05), with low median gradings of less than 0.5 observed for all areas assessed. There were no solution-related staining reactions observed with either CL type. The asmofilcon A and senofilcon A CLs were both rated highly with respect to overall comfort, with medians of 14 or 15 hours of comfortable lens wearing time per day reported at each of the study visits (p>0.05). Conclusions: Over 6 months of EW, the asmofilcon A and senofilcon A CLs performed in a similar manner with respect to visual acuity, ocular health and CL performance measures. Some changes over time were observed with both CL types, including reduced LCDVA and increased superior palpebral injection, which warrant further investigation in longer-term EW studies. Asmofilcon A appeared to be equivalent in performance to senofilcon A.

Analysis of Rail Ends under Wheel Contact Loading

The effect of the discontinuity of the rail ends and the presence of lower modulus insulation material at the gap to the variations of stresses in the insulated rail joint (IRJ) is presented. A three-dimensional wheel – rail contact model in the finite element framework is used for the analysis. It is shown that the maximum stress occurs in the subsurface of the railhead when the wheel contact occurs far away from the rail end and migrates to the railhead surface as the wheel approaches the rail end; under this condition, the interface between the rail ends and the insulation material has suffered significantly increased levels of stress concentration. The ratio of the elastic modulus of the railhead and insulation material is found to alter the levels of stress concentration. Numerical result indicates that a higher elastic modulus insulating material can reduce the stress concentration in the railhead but will generate higher stresses in the insulation material, leading to earlier failure of the insulation material

Piecing together an integrative taxonomic puzzle: microsatellite, wing shape and aedeagus length analyses of Bactrocera dorsalis s.l. (Diptera: Tephritidae) find no evidence of multiple lineages in a proposed contact zone along the Thai/Malay Peninsula

Bactrocera dorsalis (Hendel) and B. papayae Drew & Hancock represent a closely related sibling species pair for which the biological species limits are unclear; i.e., it is uncertain if they are truely two biological species, or one biological species which has been incorrectly taxonomically split. The geographic ranges of the two taxa are thought to abut or overlap on or around the Isthmus of Kra, a recognised biogeographic barrier located on the narrowest portion of the Thai Peninsula. We collected fresh material of B. dorsalis sensu lato (i.e., B. dorsalis sensu stricto + B. papayae) in a north-south transect down the Thai Peninsula, from areas regarded as being exclusively B. dorsalis s.s., across the Kra Isthmus, and into regions regarded as exclusively B. papayae. We carried out microsatellite analyses and took measurements of male genitalia and wing shape. Both the latter morphological tests have been used previously to separate these two taxa. No significant population structuring was found in the microsatellite analysis and results were consistent with an interpretation of one, predominantly panmictic population. Both morphological datasets showed consistent, clinal variation along the transect, with no evidence for disjunction. No evidence in any tests supported historical vicariance driven by the Isthmus of Kra, and none of the three datasets supported the current taxonomy of two species. Rather, within and across the area of range overlap or abutment between the two species, only continuous morphological and genetic variation was recorded. Recognition that morphological traits previously used to separate these taxa are continuous, and that there is no genetic evidence for population segregation in the region of suspected species overlap, is consistent with a growing body of literature that reports no evidence of biological differentiation between these taxa.

Attunement to haptic information helps skilled performers select implements for striking a ball in cricket

This study examined the perceptual attunement of relatively skilled individuals to physical properties of striking implements in the sport of cricket. We also sought to assess whether utilising bats of different physical properties influenced performance of a specific striking action: the front foot straight drive. Eleven, skilled male cricketers (mean age = 16.6 ± 0.3 years) from an elite school cricket development programme consented to participate in the study. Whist blindfolded, participants wielded six bats exhibiting different mass and moment of inertia (MOI) characteristics and were asked to identify their three most preferred bats for hitting a ball to a maximum distance by performing a front foot straight drive (a common shot in cricket). Next, participants actually attempted to hit balls projected from a ball machine using each of the six bat configurations to enable kinematic analysis of front foot straight drive performance with each implement. Results revealed that, on first choice, the two bats with the smallest mass and MOI values (1 and 2) were most preferred by almost two-thirds (63.7%) of the participants. Kinematic analysis of movement patterns revealed that bat velocity, step length and bat-ball contact position measures significantly differed between bats. Data revealed how skilled youth cricketers were attuned to the different bat characteristics and harnessed movement system degeneracy to perform this complex interceptive action.

Designing a self-service technology to increase self-efficacy and maintain breastfeeding

Despite the significant health benefits attributed to breastfeeding, rates in countries, such as Australia, continue to remain static or to decline. Typically, the tangible support offered for women to support breastfeeding behaviours takes the form of face-to-face advice from health professionals, peer counselling via not-for-profit organizations such as the ABA, and provision of information through websites, pamphlets, and books. Prior research indicates that face-to-face support is more effective than telephone contact (Britton, McCormic, Renfrew, Wade, & King, 2009). Given the increasing costs associated with the provision of personalized face-to-face professional support and the need for some women to maximize privacy, discretion, and judgment-free consultations, there is a gap that could be filled by the use of m-technologies such as text messaging and other social media. The research team developed MumBubConnect; a two-way SMS system which combined the personalized aspects of face-to-face contact but maintained levels of privacy. The use of SMS was immediate, portable, and overcame many of the barriers associated with embarrassment. An Page 205 of 312 online survey of 130 breastfeeding mothers indicated that MumBubConnect facilitated the seeking of social support using m-technology, increased self-efficacy and maintained the desire behaviour.

Using a design led approach to emotional business modelling

Prototyping is an established and accepted practice used by the design community. Prototypes play a valuable role during the design process and can greatly affect the designed outcome. The concept of a business model prototype, however, is not well understood by the design and business communities. Design industry trends indicate a move away from product and service innovation towards business model innovation. Therefore, it stands to reason that the role of prototypes and prototyping in this context should also be considered. This paper is conceptual and presents a process for creating and enabling business model prototypes. Specifically, the focus is on building emotional connections across the value chain to enable internal growth within firms. To do this, the authors‟ have relied on personal observations and critical reflection from multiple industry engagements. The outcomes of this critical reflective practice are presented and the opportunities and challenges for this approach are discussed. Future research opportunities are also detailed and presented within the context of the emotional business model.

Contraceptive changes after reproductive events among Australian women born in 1973 to 1978: A longitudinal study from 1996 to 2009

Background Women change contraception as they try to conceive, space births, and limit family size. This longitudinal analysis examines contraception changes after reproductive events such as birth, miscarriage or termination among Australian women born from 1973 to 1978 to identify potential opportunities to increase the effectiveness of contraceptive information and service provision. Methods Between 1996 and 2009, 5,631 Australian women randomly sampled from the Australian universal health insurance (Medicare) database completed five self-report postal surveys. Three longitudinal logistic regression models were used to assess the associations between reproductive events (birth only, birth and miscarriage, miscarriage only, termination only, other multiple events, and no new event) and subsequent changes in contraceptive use (start using, stop using, switch method) compared with women who continued to use the same method. Results After women experienced only a birth, or a birth and a miscarriage, they were more likely to start using contraception. Women who experienced miscarriages were more likely to stop using contraception. Women who experienced terminations were more likely to switch methods. There was a significant interaction between reproductive events and time indicating more changes in contraceptive use as women reach their mid-30s. Conclusion Contraceptive use increases after the birth of a child, but decreases after miscarriage indicating the intention for family formation and spacing between children. Switching contraceptive methods after termination suggests these pregnancies were unintended and possibly due to contraceptive failure. Women’s contact with health professionals around the time of reproductive events provides an opportunity to provide contraceptive services.

Challenges for researchers investigating contraceptive use and pregnancy intentions of young women living in urban and rural Australia : face-to-face discussions to increase participation in a web-based survey

Background: It is imperative to understand how to engage young women in research about issues that are important to them. There is limited reliable data on how young women access contraception in Australia especially in rural areas where services may be less available. Objective: This paper identifies the challenges involved in engaging young Australian women aged 18-23 years to participate in a web-based survey on contraception and pregnancy and ensure their ongoing commitment to follow-up web-based surveys. Methods: A group of young women, aged 18-23 years and living in urban and rural New South Wales, Australia, were recruited to participate in face-to-face discussions using several methods of recruitment: direct contact (face-to-face, telephone or email)and snowball sampling by potential participants inviting their friends. All discussions were transcribed verbatim and analyzed using thematic analysis. Results: Twenty young women participated (urban, n=10: mean age 21.6 years; rural, n=10: 20.0 years) and all used computers or smart phones to access the internet on a daily basis. All participants were concerned about the cost of internet access and utilized free access to social media on their mobile phones. Their willingness to participate in a web-based survey was dependent on incentives with a preference for small financial rewards. Most participants were concerned about their personal details and survey responses remaining confidential and secure. The most appropriate survey would take up to 15 minutes to complete, be a mix of short and long questions and eye-catching with bright colours. Questions on the sensitive topics of sexual activity, contraception and pregnancy were acceptable if they could respond with “I prefer not to answer”. Conclusions: There are demographic, participation and survey design challenges in engaging young women in a web-based survey. Based on our findings, future research efforts are needed to understand the full extent of the role social media and incentives play in the decision of young women to participate in web-based research.

Corneal sensitivity is related to established measures of diabetic peripheral neuropathy

Purpose:  The objective was to investigate the association between corneal sensitivity and established measures of diabetic peripheral neuropathy (DPN). Methods:  Corneal sensitivity was measured in 93 individuals with diabetes, 146 diabetic individuals without neuropathy and 61 control individuals without diabetes or neuropathy using a non-contact corneal aesthesiometer at the baseline visit of a five-year longitudinal natural history study of DPN. The correlation between corneal sensitivity and established measures of neuropathy was estimated and multi-dimensional scaling was used to represent similarities and dissimilarities between variables. Results:  The corneal sensitivity threshold was significantly correlated with a majority of established measures of DPN. Correlation coefficients ranged from -0.32 to 0.26. Using multi-dimensional scaling, non-contact corneal aesthesiometry was closer to the neuropathy disability score, diabetic neuropathy symptom score and Neuropad and most dissimilar to electrophysiological parameters and quantitative sensory testing. Conclusion:  Corneal sensitivity, although not strongly related, is associated with other functional measures of DPN and might provide a useful adjunct in identifying functional loss of small nerve fibre integrity.

Encouraging learners to drive using game elements and smartphones

Young drivers aged 17-24 years are at a risk of death and injury from road crashes primarily due to their age and inexperience on the road. Our research aims to investigate if a gamified mobile tracking and intervention tool can help to address this issue. We aim to build a smartphone application to support the current process of logging driving hours using a physical logbook and pen in Queensland. This provides an easier way to log driving hours than recording them in a logbook. In an attempt to engage Learners and encourage them to undertake more diverse driving practice we will explore how game elements can be integrated into the experience to motivate Learners. Previous research in other domains has shown that framing tasks as game-like can help engage and motivate users, however the addition of game elements to this space provides some interesting design challenges. This paper presents an overview of the research and presents these challenges for further discussion.

Bicep femoris voluntary activation deficits contribute to eccentric knee flexor weakness following intermittent running

INTRODUCTION: Hamstring strain injuries (HSI) are the predominant non-contact injury in many sports. Eccentric hamstring muscle weakness following intermittent running has been implicated within the aetiology of HSI. This weakness following intermittent running is often greater eccentrically than concentrically, however the cause of this unique, contraction mode specific phenomenon is unknown. AIM: To determine if this preferential eccentric decline in strength is caused by declines in voluntary hamstring muscle activation. METHODS: Fifteen recreationally active males completed 18 × 20m overground sprints. Maximal strength (concentric and eccentric knee flexor and concentric knee extensor) was determined isokinetically at the velocities of ±1800.s-1 and ±600.s- while hamstring muscle activation was assessed using surface electromyography, before and 15 minutes after the running protocol. RESULTS: Overground intermittent running caused greater eccentric (27.2 Nm; 95% CI = 11.2 to 43.3; p=0.0001) than concentric knee flexor weakness (9.3 Nm; 95% CI = -6.7 to 25.3; P=0.6361). Following the overground running, voluntary activation levels of the lateral hamstrings showed a significant decline (0.08%; 95% CI = 0.045 to 0.120; P<0.0001). In comparison, medial hamstring activation showed no change following intermittent running. CONCLUSION: Eccentric hamstring strength is decreased significantly following intermittent overground running. Voluntary activation deficits in the biceps femoris muscle are responsible for some portion of this weakness. The implications of this finding are significant because the biceps femoris muscle is the most frequently strained of all the hamstring muscles and because fatigue appears to play an important part in injury occurrence.

Do voluntary activation deficits contribute to eccentric weakness following intermittent running?

Hamstring strain injuries (HSI) are the predominant non-contact injury in many sports. Eccentric hamstring muscle weakness following intermittent running has been implicated within the aetiology of HSI. This weakness following intermittent running is often greater eccentrically than concentrically, however the cause of this unique, contraction mode specific phenomenon is unknown. PURPOSE: To determine if this preferential eccentric decline in strength is caused by declines in voluntary hamstring muscle activation. METHODS: Fifteen recreationally active males completed 18 × 20m overground sprints. Maximal strength (concentric and eccentric knee flexor and concentric knee extensor) was determined isokinetically at the velocities of ±1800.s-1 and ±600.s- while hamstring muscle activation was assessed using surface electromyography, before and 15 minutes after the running protocol. RESULTS: Overground intermittent running caused greater eccentric (27.2 Nm; 95% CI = 11.2 to 43.3; p=0.0001) than concentric knee flexor weakness (9.3 Nm; 95% CI = -6.7 to 25.3; P=0.6361). Following the overground running, voluntary activation levels of the lateral hamstrings showed a significant decline (0.08%; 95% CI = 0.045 to 0.120; P<0.0001). In comparison, medial hamstring activation showed an increased level of activation following intermittent running (0.12%; 95% CI = 0.049 to 0.030; P = 0.0102). CONCLUSION: Eccentric hamstring strength is decreased significantly following intermittent overground running. Voluntary activation deficits in the biceps femoris muscle are responsible for some portion of this weakness. The implications of this finding are significant because the biceps femoris muscle is the most frequently strained of all the hamstring muscles and because fatigue appears to play an important part in injury occurrence.

Declines in eccentric knee flexor weakness following repeat sprint running are related to declines in biceps femoris voluntary activation

Introduction: Hamstring strain injuries (HSI) are the predominant non-contact injury in many sports. Eccentric hamstring muscle weakness following intermittent running has been implicated within the aetiology of HSI. This weakness following intermittent running is sometimes greater eccentrically than concentrically, however the cause of this unique, contraction mode specific phenomenon is unknown. The purpose of this research was to determine whether declines in knee flexor strength following overground repeat sprints are caused by declines in voluntary activation of the hamstring muscles. Methods: Seventeen recreationally active males completed 3 sets of 6 by 20m overground sprints. Maximal isokinetic concentric and eccentric knee flexor and concentric knee extensor strength was determined at ±1800.s-1 and ±600.s-1 while hamstring muscle activation was assessed using surface electromyography, before and 15 minutes after the running protocol. Results: Overground repeat sprint running resulted in a significant decline in eccentric knee flexor strength (31.1 Nm; 95% CI = 21.8 to 40.3 Nm; p < 0.001). However, concentric knee flexor strength was not significantly altered (11.1 Nm; 95% CI= -2.8 to 24.9; p=0.2294). Biceps femoris voluntary activation levels displayed a significant decline eccentrically (0.067; 95% CI=0.002 to 0.063; p=0.0325). However, there was no significant decline concentrically (0.025; 95% CI=-0.018 to 0.043; p=0.4243) following sprinting. Furthermore, declines in average peak torque at -1800.s-1 could be explained by changes in hamstring activation (R2 = 0.70). Moreover, it was change in the lateral hamstring muscle activity that was related to the decrease in knee flexor torque (p = 0.0144). In comparison, medial hamstring voluntary activation showed no change for either eccentric (0.06; 95% CI = -0.033 to 0.102; p=0.298) or concentric (0.09; 95% CI = -0.03 to 0.16; p=0.298) muscle actions following repeat sprinting. Discussion: Eccentric hamstring strength is decreased significantly following overground repeat sprinting. Voluntary activation deficits in the biceps femoris muscle explain a large portion of this weakness. The implications of these findings are significant as the biceps femoris muscle is the most frequently strained of the knee flexors and fatigue is implicated in the aetiology of this injury.

Corneal changes following short-term rigid contact lens wear

Purpose: The aim of this cross-over study was to investigate the changes in corneal thickness, anterior and posterior corneal topography, corneal refractive power and ocular wavefront aberrations, following the short term use of rigid contact lenses. Method: Fourteen participants wore 4 different types of contact lenses (RGP lenses of 9.5 mm and 10.5 mm diameter, and for comparison a PMMA lens of 9.5 mm diameter and a soft silicone hydrogel lens) on 4 different days for a period of 8 h on each day. Measures were collected before and after contact lens wear and additionally on a baseline day. Results: Anterior corneal curvature generally showed a flattening with both of the RGP lenses and a steepening with the PMMA lens. A significant negative correlation was found between the change in corneal swelling and central and peripheral posterior corneal curvature (all p ≤ 0.001). RGP contact lenses caused a significant decrease in corneal refractive power (hyperopic shift) of approximately 0.5 D. The PMMA contact lenses caused the greatest corneal swelling in both the central (27.92 ± 15.49 μm, p < 0.001) and peripheral (17.78 ± 12.11 μm, p = 0.001) corneal regions, a significant flattening of the posterior cornea and an increase in ocular aberrations (all p ≤ 0.05). Conclusion: The corneal swelling associated with RGP lenses was relatively minor, but there was slight central corneal flattening and a clinically significant hyperopic change in corneal refractive power after the first day of lens wear. The PMMA contact lenses resulted in significant corneal swelling and reduced optical performance of the cornea.