Two-Photon Fluorescence Microscopy Imaging of Cellular Oxidative Stress Using Profluorescent Nitroxides

A range of varying chromophore nitroxide free radicals and their nonradical methoxyamine analogues were synthesized and their linear photophysical properties examined. The presence of the proximate free radical masks the chromophore’s usual fluorescence emission, and these species are described as profluorescent. Two nitroxides incorporating anthracene and fluorescein chromophores (compounds 7 and 19, respectively) exhibited two-photon absorption (2PA) cross sections of approximately 400 G.M. when excited at wavelengths greater than 800 nm. Both of these profluorescent nitroxides demonstrated low cytotoxicity toward Chinese hamster ovary (CHO) cells. Imaging colocalization experiments with the commercially available CellROX Deep Red oxidative stress monitor demonstrated good cellular uptake of the nitroxide probes. Sensitivity of the nitroxide probes to H2O2-induced damage was also demonstrated by both one- and two-photon fluorescence microscopy. These profluorescent nitroxide probes are potentially powerful tools for imaging oxidative stress in biological systems, and they essentially “light up” in the presence of certain species generated from oxidative stress. The high ratio of the fluorescence quantum yield between the profluorescent nitroxide species and their nonradical adducts provides the sensitivity required for measuring a range of cellular redox environments. Furthermore, their reasonable 2PA cross sections provide for the option of using two-photon fluorescence microscopy, which circumvents commonly encountered disadvantages associated with one-photon imaging such as photobleaching and poor tissue penetration.

Timing of births and endometrial cancer risk in Swedish women

While a protective long-term effect of parity on endometrial cancer risk is well established, the impact of timing of births is not fully understood. We examined the relationship between endometrial cancer risk and reproductive characteristics in a population-based cohort of 2,674,465 Swedish women, 20–72 years of age. During follow-up from 1973 through 2004, 7,386 endometrial cancers were observed. Compared to uniparous women, nulliparous women had a significantly elevated endometrial cancer risk (hazard ratio [HR] = 1.32, 95% confidence interval [CI], 1.22–1.42). Endometrial cancer risk decreased with increasing parity; compared to uniparous women, women with ≥4 births had a HR=0.66 (95% CI, 0.59–0.74); p-trend < 0.001. Among multiparous women, we observed no relationship of risk with age at first birth after adjustment for other reproductive factors. While we initially observed a decreased risk with later ages at last birth, this appeared to reflect a stronger relationship with time since last birth, with women with shorter times being at lowest risk. In models for multiparous women that included number of births, age at first and last birth, and time since last birth, age at last birth was not associated with endometrial cancer risk, while shorter time since last birth and increased parity were associated with statistically significantly reduced endometrial cancer risks. The HR was 3.95 (95%CI; 2.17–7.20; p-trend=<0.0001) for women with ≥25 years since a last birth compared to women having given birth within 4 years. Our findings support that clearance of initiated cells during delivery may be important in endometrial carcinogenesis. Keywords: endometrial carcinoma, parity, registry, reproductive factors

Economic fluctuations and productivity in the Malaysian construction sector

Growth in productivity is the key determinant of the long-term health and prosperity of an economy. The construction industry being one of major strategic importance, its productivity performance has a significant effect on national economic growth. The relationship between construction output and economy has received intensive studies, but there is lack of empirical study on the relationship between construction productivity and economic fluctuations. Fluctuations in construction output are endemic in the industry. In part they are caused by the boom and slump of the economy as a whole and in part by the nature of the construction product. This research aims to uncover how the productivity of construction sector is influenced in the course of economic fluctuations in Malaysia. Malaysia has adopted three economic policies – New Economic Policy (1971-1990), National Development Policy (1991-2000) and the National Vision Policy (2001-2010) since gaining independence in 1959. The Privatisation Master Plan was introduced in 1991. Operating within this historical context, the Malaysian construction sector has experienced four business cycles since 1960. A mixed-method design approach is adopted in this study. Quantitative analysis was conducted on the published official statistics of the construction industry and the overall economy in Malaysia between 1970 and 2009. Qualitative study involved interviews with a purposive sample of 21 industrial participants. This study identified a 32-year long building cycle appears in 1975-2006. It is superimposed with three shorter construction business cycles in 1975-1987, 1987-1999 and 1999-2006. The correlations of Construction labour productivity (CLP) and GDP per capita are statistically significant for the 1975-2006 building cycle, 1987-1999 and 1999-2006 construction business cycles. It was not significant in 1975-1987 construction business cycles. The Construction Industry Surveys/Census over the period from 1996 to 2007 show that the average growth rate of total output per employee expanded but the added value per employee contracted which imply high cost of bought-in materials and services and inefficient usage of purchases. The construction labour productivity is peaked at 2004 although there is contraction of construction sector in 2004. The residential subsector performed relatively better than the other sub-sectors in most of the productivity indicators. Improvements are found in output per employee, value added per employee, labour competitiveness and capital investment but declines are recorded in value added content and capital productivity. The civil engineering construction is most productive in the labour productivity nevertheless relatively poorer in the capital productivity. The labour cost is more competitive in the larger size establishment. The added value per labour cost is higher in larger sized establishment attributed to efficient in utilization of capital. The interview with the industrial participant reveals that the productivity of the construction sector is influenced by the economic environment, the construction methods, contract arrangement, payment chain and regulatory policies. The fluctuations of construction demand have caused companies switched to defensive strategy during the economic downturn and to ensure short-term survival than to make a profit for the long-term survival and growth. It leads the company to take drastic measures to curb expenses, downsizing, employ contract employment, diversification and venture overseas market. There is no empirical evidence supports downsizing as a necessary step in a process of reviving productivity. The productivity does not correlate with size of firm. A relatively smaller and focused firm is more productive than the larger and diversified organisation. However diversified company experienced less fluctuation in both labour and capital productivity. In order to improve the productivity of the construction sector, it is necessary to remove the negatives and flaws from past practices. The recommended measures include long-term strategic planning and coordinated approaches of government agencies in planning of infrastructure development and to provide regulatory environments which encourage competition and facilitate productivity improvement.

Doing blog research

Blogs and other online platforms for personal writing such as LiveJournal have been of interest to researchers across the social sciences and humanities for a decade now. Although growth in the uptake of blogging has stalled somewhat since the heyday of blogs in the early 2000s, blogging continues to be a major genre of Internet-based communication. Indeed, at the same time that mass participation has moved on to Facebook, Twitter, and other more recent communication phenomena, what has been left behind by the wave of mass adoption is a slightly smaller but all the more solidly established blogosphere of engaged and committed participants. Blogs are now an accepted part of institutional, group, and personal communications strategies (Bruns and Jacobs, 2006); in style and substance, they are situated between the more static information provided by conventional Websites and Webpages and the continuous newsfeeds provided through Facebook and Twitter updates. Blogs provide a vehicle for authors (and their commenters) to think through given topics in the space of a few hundred to a few thousand words – expanding, perhaps, on shorter tweets, and possibly leading to the publication of more fully formed texts elsewhere. Additionally, they are also a very flexible medium: they readily provide the functionality to include images, audio, video, and other additional materials – as well as the fundamental tool of blogging, the hyperlink itself. Indeed, the role of the link in blogs and blog posts should not be underestimated. Whatever the genre and topic that individual bloggers engage in, for the most part blogging is used to provide timely updates and commentary – and it is typical for such material to link both to relevant posts made by other bloggers, and to previous posts by the present author, both to background material which provides readers with further information about the blogger’s current topic, and to news stories and articles which the blogger found interesting or worthy of critique. Especially where bloggers are part of a larger community of authors sharing similar interests or views (and such communities are often indicated by the presence of yet another type of link – in blogrolls, often in a sidebar on the blog site, which list the blogger’s friends or favourites), then, the reciprocal writing and linking of posts often constitutes an asynchronous, distributed conversation that unfolds over the course of days, weeks, and months. Research into blogs is interesting for a variety of reasons, therefore. For one, a qualitative analysis of one or several blogs can reveal the cognitive and communicative processes through which individual bloggers define their online identity, position themselves in relation to fellow bloggers, frame particular themes, topics and stories, and engage with one another’s points of view. It may also shed light on how such processes may differ across different communities of interest, perhaps in correlation with the different societal framing and valorisation of specific areas of interest, with the socioeconomic backgrounds of individual bloggers, or with other external or internal factors. Such qualitative research now looks back on a decade-long history (for key collections, see Gurak, et al., 2004; Bruns and Jacobs, 2006; also see Walker Rettberg, 2008) and has recently shifted also to specifically investigate how blogging practices differ across different cultures (Russell and Echchaibi, 2009). Other studies have also investigated the practices and motivations of bloggers in specific countries from a sociological perspective, through large-scale surveys (e.g. Schmidt, 2009). Blogs have also been directly employed within both K-12 and higher education, across many disciplines, as tools for reflexive learning and discussion (Burgess, 2006).

Evolutionary relationships and divergence times among the native rats of Australia

Background The genus Rattus is highly speciose and has a complex taxonomy that is not fully resolved. As shown previously there are two major groups within the genus, an Asian and an Australo-Papuan group. This study focuses on the Australo-Papuan group and particularly on the Australian rats. There are uncertainties regarding the number of species within the group and the relationships among them. We analysed 16 mitochondrial genomes, including seven novel genomes from six species, to help elucidate the evolutionary history of the Australian rats. We also demonstrate, from a larger dataset, the usefulness of short regions of the mitochondrial genome in identifying these rats at the species level. Results Analyses of 16 mitochondrial genomes representing species sampled from Australo-Papuan and Asian clades of Rattus indicate divergence of these two groups ~2.7 million years ago (Mya). Subsequent diversification of at least 4 lineages within the Australo-Papuan clade was rapid and occurred over the period from ~ 0.9-1.7 Mya, a finding that explains the difficulty in resolving some relationships within this clade. Phylogenetic analyses of our 126 taxon, but shorter sequence (1952 nucleotides long), Rattus database generally give well supported species clades. Conclusions Our whole mitochondrial genome analyses are concordant with a taxonomic division that places the native Australian rats into the Rattus fuscipes species group. We suggest the following order of divergence of the Australian species. R. fuscipes is the oldest lineage among the Australian rats and is not part of a New Guinean radiation. R. lutreolus is also within this Australian clade and shallower than R. tunneyi while the R. sordidus group is the shallowest lineage in the clade. The divergences within the R. sordidus and R. leucopus lineages occurring about half a million years ago support the hypotheses of more recent interchanges of rats between Australia and New Guinea. While problematic for inference of deeper divergences, we report that the analysis of shorter mitochondrial sequences is very useful for species identification in rats.

Improving trust and securing data accessibility for e-health decision making by using data encryption techniques

In the medical and healthcare arena, patients‟ data is not just their own personal history but also a valuable large dataset for finding solutions for diseases. While electronic medical records are becoming popular and are used in healthcare work places like hospitals, as well as insurance companies, and by major stakeholders such as physicians and their patients, the accessibility of such information should be dealt with in a way that preserves privacy and security. Thus, finding the best way to keep the data secure has become an important issue in the area of database security. Sensitive medical data should be encrypted in databases. There are many encryption/ decryption techniques and algorithms with regard to preserving privacy and security. Currently their performance is an important factor while the medical data is being managed in databases. Another important factor is that the stakeholders should decide more cost-effective ways to reduce the total cost of ownership. As an alternative, DAS (Data as Service) is a popular outsourcing model to satisfy the cost-effectiveness but it takes a consideration that the encryption/ decryption modules needs to be handled by trustworthy stakeholders. This research project is focusing on the query response times in a DAS model (AES-DAS) and analyses the comparison between the outsourcing model and the in-house model which incorporates Microsoft built-in encryption scheme in a SQL Server. This research project includes building a prototype of medical database schemas. There are 2 types of simulations to carry out the project. The first stage includes 6 databases in order to carry out simulations to measure the performance between plain-text, Microsoft built-in encryption and AES-DAS (Data as Service). Particularly, the AES-DAS incorporates implementations of symmetric key encryption such as AES (Advanced Encryption Standard) and a Bucket indexing processor using Bloom filter. The results are categorised such as character type, numeric type, range queries, range queries using Bucket Index and aggregate queries. The second stage takes the scalability test from 5K to 2560K records. The main result of these simulations is that particularly as an outsourcing model, AES-DAS using the Bucket index shows around 3.32 times faster than a normal AES-DAS under the 70 partitions and 10K record-sized databases. Retrieving Numeric typed data takes shorter time than Character typed data in AES-DAS. The aggregation query response time in AES-DAS is not as consistent as that in MS built-in encryption scheme. The scalability test shows that the DBMS reaches in a certain threshold; the query response time becomes rapidly slower. However, there is more to investigate in order to bring about other outcomes and to construct a secured EMR (Electronic Medical Record) more efficiently from these simulations.

Shortening cemented femoral implants. An in vitro investigation to quantify exeter femoral implant rotational stability vs simulated implant length

The Exeter stems vary in length from 90 to 150 mm. The shorter stems generally have lower offsets. The purpose of this study was to determine if length of stem, with fixed offset, affected rotational stability. Mechanical testing was carried out on 10 implant-cement constructs with 2 loading profiles, rising from chair and stair climbing, at different simulated implant lengths using purpose-built apparatus. This paper presents a mechanism for clinically observed rotational stability and explains the mechanical characteristics required for rotational stability in Exeter femoral stems. © 2012.

FGFR2 point mutations in 466 Endometrioid Endometrial Tumors : relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and Clinicopathological features

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

Methodological challenges when estimating the effects of season and seasonal exposures on birth outcomes

Background Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it. Methods To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable. Results We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C. Conclusions Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.

Effects of enhanced somatosensory information on postural stability in older people and people with Parkinson’s disease

The somatosensory system plays an important role in balance control and age-related changes to this system have been implicated in falls. Parkinson’s disease (PD) is a chronic and progressive disease of the brain, characterized by postural instability and gait disturbance. Previous research has shown that deficiencies in somatosensory feedback may contribute to the poorer postural control demonstrated by PD individuals. However, few studies have comprehensively explored differences in somatosensory function and postural control between PD participants and healthy older individuals. The soles of the feet contain many cutaneous mechanoreceptors that provide important somatosensory information sources for postural control. Different types of insole devices have been developed to enhance this somatosensory information and improve postural stability, but these devices are often too complex and expensive to integrate into daily life. Textured insoles provide a more passive intervention that may be an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. However, to date, there has been little work conducted to test the efficacy of enhanced somatosensory input induced by textured insoles in both healthy and PD populations during standing and walking. Therefore, the aims of this thesis were to determine: 1) whether textured insole surfaces can improve postural stability by enhancing somatosensory information in younger and older adults, 2) the differences between healthy older participants and PD participants for measures of physiological function and postural stability during standing and walking, 3) how changes in somatosensory information affect postural stability in both groups during standing and walking; and 4), whether textured insoles can improve postural stability in both groups during standing and walking. To address these aims, Study 1 recruited seven older individuals and ten healthy young controls to investigate the effects of two textured insole surfaces on postural stability while performing standing balance tests on a force plate. Participants were tested under three insole surface conditions: 1) barefoot; 2) standing on a hard textured insole surface; and 3), standing on a soft textured insole surface. Measurements derived from the centre of pressure displacement included the range of anterior-posterior and medial-lateral displacement, path length and the 90% confidence elliptical area (C90 area). Results of study 1 revealed a significant Group*Surface*Insole interaction for the four measures. Both textured insole surfaces reduced postural sway for the older group, especially in the eyes closed condition on the foam surface. However, participants reported that the soft textured insole surface was more comfortable and, hence, the soft textured insoles were adopted for Studies 2 and 3. For Study 2, 20 healthy older adults (controls) and 20 participants with Parkinson’s disease were recruited. Participants were evaluated using a series of physiological assessments that included touch sensitivity, vibratory perception, and pain and temperature threshold detection. Furthermore, nerve function and somatosensory evoked potentials tests were utilized to provide detailed information regarding peripheral nerve function for these participants. Standing balance and walking were assessed on different surfaces using a force plate and the 3D Vicon motion analysis system, respectively. Data derived from the force plate included the range of anterior-posterior and medial-lateral sway, while measures of stride length, stride period, cadence, double support time, stance phase, velocity and stride timing variability were reported for the walking assessment. The results of this study demonstrated that the PD group had decrements in somatosensory function compared to the healthy older control group. For electrodiagnosis, PD participants had poorer nerve function than controls, as evidenced by slower nerve conduction velocities and longer latencies in sural nerve and prolonged latency in the P37 somatosensory evoked potential. Furthermore, the PD group displayed more postural sway in both the anterior-posterior and medial-lateral directions relative to controls and these differences were increased when standing on a foam surface. With respect to the gait assessment, the PD group took shorter strides and had a reduced stride period compared with the control group. Furthermore, the PD group spent more time in the stance phase and had increased cadence and stride timing variability than the controls. Compared with walking on the firm surface, the two groups demonstrated different gait adaptations while walking on the uneven surface. Controls increased their stride length and stride period and decreased their cadence, which resulted in a consistent walking velocity on both surfaces. Conversely, while the PD patients also increased their stride period and decreased their cadence and stance period on the uneven surface, they did not increase their stride length and, hence walked slower on the uneven surface. In the PD group, there was a strong positive association between decreased somatosensory function and decreased clinical balance, as assessed by the Tinetti test. Poorer somatosensory function was also strongly positively correlated with the temporospatial gait parameters, especially shorter stride length. Study 3 evaluated the effects of manipulating the somatosensory information from the plantar surface of the feet using textured insoles in the same populations assessed in Study 2. For this study, participants performed the standing and walking balance tests under three footwear conditions: 1) barefoot; 2) with smooth insoles; and 3), with textured insoles. Standing balance and walking were evaluated using a force plate and a Vicon motion analysis system and the data were analysed in the same way outlined for Study 2. The findings showed that the smooth and textured insoles caused different effects on postural control during both the standing and walking trials. Both insoles decreased medial-lateral sway to the same level on the firm surface. The greatest benefits were observed in the PD group while wearing the textured insole. When standing under a more challenging condition on the foam surface with eyes closed, only the textured insole decreased medial-lateral sway in the PD group. With respect to the gait trials, both insoles increased walking velocity, stride length and stride time and decreased cadence, but these changes were more pronounced for the textured insoles. The effects of the textured insoles were evident under challenging conditions in the PD group and increased walking velocity and stride length, while decreasing cadence. Textured insoles were also effective in reducing the time spent in the double support and stance phases of the gait cycle and did not increase stride timing variability, as was the case for the smooth insoles for the PD group. The results of this study suggest that textured insoles, such as those evaluated in this research, may provide a low-cost means of improving postural stability in high-risk groups, such as people with PD, which may act as an important intervention to prevent falls.

Monocular amblyopia and higher order aberrations

This study compared the corneal and total higher order aberrations between the fellow eyes in monocular amblyopia. Nineteen amblyopic subjects (8 refractive and 11 strabismic) (mean age 30 ± 11 years) were recruited. A range of biometric and optical measurements were collected from the amblyopic and non-amblyopic eye including; axial length, corneal topography and total higher order aberrations. For a sub-group of eleven non-presbyopic subjects (6 refractive and 5 strabismic amblyopes, mean age 29 ± 10 years) total higher order aberrations were also measured during accommodation (2.5 D stimuli). Amblyopic eyes were significantly shorter and more hyperopic compared to non-amblyopic eyes and the interocular difference in axial length correlated with both the magnitude of anisometropia and amblyopia (both p < 0.01). Significant differences in higher order aberrations were observed between fellow eyes, which varied with the type of amblyopia. Refractive amblyopes displayed higher levels of 4th order corneal aberrations C(4, 0)(spherical aberration), C(4, 2)(secondary astigmatism 90°) and C(4, −2)(secondary astigmatism along 45°) in the amblyopic eye compared to the non-amblyopic eye. Strabismic amblyopes exhibited significantly higher levels of C(3, 3)(trefoil) in the amblyopic eye for both corneal and total higher order aberrations. During accommodation, the amblyopic eye displayed a significantly greater lag of accommodation compared to the non-amblyopic eye, while the changes in higher order aberrations were similar in magnitude between fellow eyes. Asymmetric visual experience during development appears to be associated with asymmetries in higher order aberrations, in some cases proportional to the magnitude of anisometropia and dependent upon the amblyogenic factor.

Ownership structure and concentration and the timeliness of corporate earnings : Malaysian evidence

This thesis provides the first evidence on how ownership concentration and structure relate to the timeliness of price discovery and reporting lags in Malaysia. Based on a sample of 1,276 Malaysian firms from 1996 to 2009, the results show that ownership concentration and the identity of the largest shareholder matter to the timeliness of price discovery and reporting lags. Specifically, closely-held firms are more timely in their price discovery and have shorter reporting lags, particularly if the largest shareholder is a foreigner or a financial institution. Government-owned firms have longer reporting lags, as expected, but we find no evidence that family-owned firms have significantly different timeliness of price discovery and reporting lags than other firms. Additional analysis shows that prior to the implementation of the Malaysian Code of Corporate Governance, firms were more timely in their price discovery but longer in their reporting lag.

Built to last versus meant to end : time bounds specification in strategic alliances

This article explores an important temporal aspect of the design of strategic alliances by focusing on the issue of time bounds specification. Time bounds specification refers to a choice on behalf of prospective alliance partners at the time of alliance formation to either pre-specify the duration of an alliance to a specific time window, or to keep the alliance open-ended (Reuer & Ariňo, 2007). For instance, Das (2006) mentions the example of the alliance between Telemundo Network and Mexican Argos Comunicacion (MAC). Announced in October 2000, this alliance entailed a joint production of 1200 hours of comedy, news, drama, reality and novella programs (Das, 2006). Conditioned on the projected date of completing the 1200 hours of programs, Telemundo Network and MAC pre-specified the time bounds of the alliance ex ante. Such time-bound alliances are said to be particularly prevalent in project-based industries, like movie production, construction, telecommunications and pharmaceuticals (Schwab & Miner, 2008). In many other instances, however, firms may choose to keep their alliances open-ended, not specifying a specific time bound at the time of alliance formation. The choice between designing open-ended alliances that are “built to last”, versus time bound alliances that are “meant to end” is important. Seminal works like Axelrod (1984), Heide & Miner (1992), and Parkhe (1993) demonstrated that the choice to place temporal bounds on a collaborative venture has important implications. More specifically, collaborations that have explicit, short term time bounds (i.e. what is termed a shorter “shadow of the future”) are more likely to experience opportunism (Axelrod, 1984), are more likely to focus on the immediate present (Bakker, Boros, Kenis & Oerlemans, 2012), and are less likely to develop trust (Parkhe, 1993) than alliances for which time bounds are kept indeterminate. These factors, in turn, have been shown to have important implications for the performance of alliances (e.g. Kale, Singh & Perlmutter, 2000). Thus, there seems to be a strong incentive for organizations to form open-ended strategic alliances. And yet, Reuer & Ariňo (2007), one of few empirical studies that details the prevalence of time-bound and open-ended strategic alliances, found that about half (47%) of the alliances in their sample were time bound, the other half were open-ended. What conditions, then, determine this choice?

How important is length? : mechanical testing and measurement of a cemented, polished, tapered femoral implant

Total hip arthroplasty (THA) has a proven clinical record for providing pain relief and return of function to patients with disabling arthritis. There are many successful options for femoral implant design and fixation. Cemented, polished, tapered femoral implants have been shown to have excellent results in national joint registries and long-term clinical series. These implants are usually 150mm long at their lateral aspect. Due to their length, these implants cannot always be offered to patients due to variations in femoral anatomy. Polished, tapered implants as short as 95mm exist, however their small proximal geometry (neck offset and body size) limit their use to smaller stature patients. There is a group of patients in which a shorter implant with a maintained proximal body size would be advantageous. There are also potential benefits to a shorter implant in standard patient populations such as reduced bone removal due to reduced reaming, favourable loading of the proximal femur, and the ability to revise into good proximal bone stock if required. These factors potentially make a shorter implant an option for all patient populations. The role of implant length in determining the stability of a cemented, polished, tapered femoral implant is not well defined by the literature. Before changes in implant design can be made, a better understanding of the role of each region in determining performance is required. The aim of the thesis was to describe how implant length affects the stability of a cemented, polished, tapered femoral implant. This has been determined through an extensive body of laboratory testing. The major findings are that for a given proximal body size, a reduction in implant length has no effect on the torsional stability of a polished, tapered design, while a small reduction in axial stability should be expected. These findings are important because the literature suggests that torsional stability is the major determinant of long-term clinical performance of a THA system. Furthermore, a polished, tapered design is known to be forgiving of cement-implant interface micromotion due to the favourable wear characteristics. Together these findings suggest that a shorter polished, tapered implant may be well tolerated. The effect of a change in implant length on the geometric characteristics of polished, tapered design were also determined and applied to the mechanical testing. Importantly, interface area does play a role in stability of the system; however it is the distribution of the interface and not the magnitude of the area that defines stability. Taper angle (at least in the range of angles seen in this work) was shown not to be a determinant of axial or torsional stability. A range of implants were tested, comparing variations in length, neck offset and indication (primary versus cement-in-cement revision). At their manufactured length, the 125mm implants were similar to their longer 150mm counterparts suggesting that they may be similarly well tolerated in the clinical environment. However, the slimmer cement-in-cement revision implant was shown to have a poorer mechanical performance, suggesting their use in higher demand patients may be hazardous. An implant length of 125mm has been shown to be quite stable and the results suggest that a further reduction to 100mm may be tolerated. However, further work is required. A shorter implant with maintained proximal body size would be useful for the group of patients who are unable to access the current standard length implants due to variations in femoral anatomy. Extending the findings further, the similar function with potential benefits of a shorter implant make their application to all patients appealing.

Exeter short stems compared with standard length Exeter stems : experience from the Australian Orthopaedic Association National Joint Replacement Registry

The standard Exeter stem has a length of 150mm with offsets 37.5mm to 56mm. Shorter stems of lengths 95mm, 115mm and 125mm with offsets 35.5mm or less are available for patients with smaller femurs. Concern has been raised regarding the behaviour of the smaller implants. This paper analysed data from the Australian Orthopaedic Association National Joint Replacement Registry comparing survivorship of stems of offset 35.5mm or less with the standard stems of 37.5mm offset or greater. At seven years there was no significant difference in the Cumulative Percent Revision Rate in the short stems (3.4%, 95% CI 2.4-4.8%) compared with the standard length stems (3.5%, 95% CI 3.3-3.8%) despite its use in a greater proportion of potentially more difficult developmental dysplasia of the hip cases.