Walking ability of individuals with transfemoral amputation fitted with osseointegrated implant

The prosthetic benefits of osseointegrated fixation for individuals with limb loss, particularly those with transfemoral amputation (TFA), have been clearly demonstrated in the literature. However, very little information is currently available to established how this prosthetic benefits are translated into functional outcomes and, more precisely, walking abilities [1-3]. The ultimate aim of this presentation was to explore how walking abilities of a TFA fitted with an OPRA fixation could be assess through typical temporal and spatial gait characteristics[2].

Direct measurement as a tool for assessing the accuracy of inverse dynamics

The understanding of the loads generated within the prosthetic leg can aid engineers in the design of components and clinicians in the process of rehabilitation. Traditional methods to assess these loads have relied on inverse dynamics. This indirect method estimates the applied load using video recordings and force-plates located at a distance from the region of interest, such as the base of the residuum. The well-known limitations of this method are related to the accuracy of this recursive model and the experimental conditions required (Frossard et al., 2003). Recent developments in sensors (Frossard et al., 2003) and prosthetic fixation (Brånemark et al., 2000) permit the direct measurement of the loads applied on the residuum of transfemoral amputees. In principle, direct measurement should be an appropriate tool for assessing the accuracy of inverse dynamics. The purpose of this paper is to determine the validity of this assumption. The comparative variable used in this study is the velocity of the relative body center of mass (VCOM(t)). The relativity is used to align the static (w.r.t. position) force plate measurement with the dynamic load cell measurement.

One step closer into the design of fall protective device for individuals fitted with a bone-anchored prosthesis

The consequences of falls are often dreadful for individuals with lower limb amputation using bone-anchored prosthesis.[1-5] Typically, the impact on the fixation is responsible for bending the intercutaneous piece that could lead to a complete breakage over time. .[3, 5-8] The surgical replacement of this piece is possible but complex and expensive. Clearly, there is a need for solid data enabling an evidence-based design of protective devices limiting impact forces and torsion applied during a fall. The impact on the fixation during an actual fall is obviously difficult to record during a scientific experiment.[6, 8-13] Consequently, Schwartze and colleagues opted for one of the next best options science has to offer: simulation with an able-bodied participant. They recorded body movements and knee impacts on the floor while mimicking several plausible falling scenarios. Then, they calculated the forces and moments that would be applied at four levels along the femur corresponding to amputation heights.[6, 8-11, 14-25] The overall forces applied during the falls were similar regardless of the amputation height indicating that the impact forces were simply translated along the femur. As expected, they showed that overall moments generally increased with amputation height due to changes in lever arm. This work demonstrates that devices preventing only against force overload do not require considering amputation height while those protecting against bending moments should. Another significant contribution is to provide, for the time, the magnitude of the impact load during different falls. This loading range is crucial to the overall design and, more precisely, the triggering threshold of protective devices. Unfortunately, the analysis of only a single able-bodied participant replicating falls limits greatly the generalisation of the findings. Nonetheless, this case study is an important milestone contributing to a better understanding of load impact during a fall. This new knowledge will improve the treatment, the safe ambulation and, ultimately, the quality of life of individuals fitted with bone-anchored prosthesis.

Bone-anchored prosthesis: Evidence that “gains” overcome the “pain”

Most of socket related discomforts leading to a significant decrease in quality of life of individuals with limb amputation can be overcome by surgical techniques enabling bone-anchored prostheses. To date, the OPRA two-stage procedure (i.e., S1, S2) is the most acknowledged treatment. However, surgical implantations of osseointegrated fixations are developing at an unprecedented pace worldwide.[1-18] Clearly, this option is becoming accessible to a wide range of individuals with limb amputations. The team led by Dr Rickard Branemark has published a number of landmark articles each focusing on a particular aspect (e.g., health related quality of life, functional outcomes, bone remodelling, infection rate). [1-3, 19-32] However, evidences presented in this prospective study are remarkable. Functional outcome, health-related quality of life and complications were considered concurrently for a large population (i.e., 51 participants) over an extended period of time (i.e., up to year follow up). Therefore, the “gain” and “pain” of the whole procedure were truly contrasted for the first time. The results confirmed that OPRA surgical and rehabilitation procedures improved significantly prosthetic use, mobility, global situation and fewer problems. Furthermore, the authors reported 47 episodes of infections for 63% (32) participants between post-op S1 and two years follow up. A total of 87% (41) were superficial infections recorded for 28 participants between post-op S2 and two years follow up, while 13% (6) were deep infections occurring for 4 participants during post-op S1 and S2. As expected, post-op S2 phase was the most prone to both infections. More importantly, the vast majority of infections were effectively treated with oral antibiotics. Clearly, this study provided definitive evidence that the benefits of OPRA fixation overcome complications. This article is also establishing reporting standards and benchmark data for future studies focusing on bone-anchored prostheses.

Safety of OPRA procedure for individuals with upper limb amputation

Surgical implantations of osseointegrated fixations for bone-anchored prosthesis are developing at an unprecedented pace worldwide while initial skepticism in the orthopedic community is slowly fading away. Clearly, this option is becoming accessible to a wide range of individuals with limb loss. [1-18] The team led by Dr Rickard Branemark has previously published a number of landmark articles focusing on the benefits and safety of the OPRA fixation mainly for individual with lower limb loss, particularly those with transfemoral amputation. [1-3, 19-32] However, similar information is lacking for those with upper limb amputation. This team is once again taking a leading role by sharing a retrospective study focusing on the implant survival, adverse events, implant stability, and bone remodelling for 18 individuals with transhumeral amputation over a 5-year post-operative period. Therefore, a comprehensive analysis of the safety of the procedure is accessible for the first time. In essence, the results showed an implant survival rate of 83% and 80% at 2 and 5 year follow ups, respectively. The most frequent adverse events were superficial skin infections that occurred for 28% (5) participants while the least frequent was deep bone infection that happened only once. More importantly, 38% of complications due to infections were effectively managed with nonoperative treatments (e.g., revision of skin penetration site, local cleaning, antibiotics, restriction of soft tissue mobility). Implant stability and bone remodelling were satisfactory. Clearly, this study provided better understanding of the safety of the OPRA surgical and rehabilitation procedure for individuals with upper limb amputation while establishing standards and benchmark data for future studies. However, strong evidences of the benefits are yet to be demonstrated. However, increase in health related quality of life and functional outcomes (e.g., range of movement) are likely. Altogether, the team of authors are providing further evidence that bone-anchored attachment is definitely a promising alternative to socket prostheses.

Effects of anticoagulants on outcome of femoral neck fracture surgery

PURPOSE To review records of 330 patients who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy. METHODS Medical records of 235 women and 95 men aged 48 to 103 years (mean, 81.6; standard deviation [SD], 13.1) who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy were reviewed. 30 patients were on warfarin, 105 on aspirin, 28 on clopidogrel, and 167 were controls. The latter 3 groups were combined as the non-warfarin group and compared with the warfarin group. Hospital mortality, time from admission to surgery, length of hospital stay, return to theatre, and postoperative complications (wound infection, deep vein thrombosis, and pulmonary embolism) were assessed. RESULTS The warfarin and control groups were significantly younger than the clopidogrel and aspirin groups (80.8 vs. 80.0 vs. 84.2 vs. 83.7 years, respectively, p<0.05). 81% of the patients underwent surgery within 48 hours of admission. The overall mean time from admission to surgery was 1.8 days; it was longer in the warfarin than the aspirin, clopidogrel, and control groups (3.3 vs. 1.8 vs. 1.6 vs. 1.6 days, respectively, p<0.001). The mean length of hospital stay was 17.5 (SD, 9.6; range, 3-54) days. The overall hospital mortality was 3.9%; it was 6.7% in the warfarin group, 3.8% in the aspirin group, 3.6% in the clopidogrel group, and 3.6% in the control group (p=0.80). Four patients returned to theatre for surgery: one in the warfarin group for washout of a haematoma, 2 in the aspirin group for repositioning of a mal-fixation and for debridement of wound infection, and one in the control group for debridement of wound infection. The warfarin group did not differ significantly from non-warfarin group in terms of postoperative complication rate (6.7% vs. 2.7%, p=0.228) and the rate of return to theatre (3.3% vs. 1%, p=0.318). CONCLUSION It is safe to continue aspirin and clopidogrel prior to surgical treatment for femoral neck fracture. The risk of delaying surgery outweighs the peri-operative bleeding risk.

From ImageNet to mining: Adapting visual object detection with minimal supervision

This paper presents visual detection and classification of light vehicles and personnel on a mine site.We capitalise on the rapid advances of ConvNet based object recognition but highlight that a naive black box approach results in a significant number of false positives. In particular, the lack of domain specific training data and the unique landscape in a mine site causes a high rate of errors. We exploit the abundance of background-only images to train a k-means classifier to complement the ConvNet. Furthermore, localisation of objects of interest and a reduction in computation is enabled through region proposals. Our system is tested on over 10km of real mine site data and we were able to detect both light vehicles and personnel. We show that the introduction of our background model can reduce the false positive rate by an order of magnitude.

Lipid-modified azurin of Neisseria meningitidis is a copper protein localized on the outer membrane surface and not regulated by FNR

The laz gene of Neisseria meningitidis is predicted to encode a lipid-modified azurin (Laz). Laz is very similar to azurin, a periplasmic protein, which belongs to the copper-containing proteins in the cupredoxin superfamily. In other bacteria, azurin is an electron donor to nitrite reductase, an important enzyme in the denitrifying process. It is not known whether Laz could function as an electron transfer protein in this important pathogen. Laz protein was heterologously expressed in Escherichia coli and purified. Electrospray mass spectrometry indicated that the Laz protein contains one copper ion. Laz was shown to be redox-active in the presence of its redox center copper ion. When oxidized, Laz exhibits an intense blue colour and absorbs visible light around 626 nm. The absorption is lost when exposed to diethyldithiocarbamate, a copper chelating agent. Polyclonal antibodies were raised against purified Laz for detecting expression of Laz under different growth conditions and to determine the orientation of Laz on the outer membrane. The expression of Laz under microaerobic and microaerobic denitrifying conditions was slightly higher than that under aerobic conditions. However, the expression of Laz was similar between the wild type strain and an fnr mutant, suggesting that Fumarate/Nitrate reduction regulator (FNR) does not regulate the expression of Laz despite the presence of a partial FNR box upstream of the laz gene. We propose that some Laz protein is exposed on the outer membrane surface of N. meningitidis as the αLaz antibodies can increase killing by complement in a capsule deficient N. meningitidis strain, in a dose-dependent fashion.

Modulating exercise-induced hormesis: Does less equal more?

Hormesis enco 16 mpasses the notion that low levels of stress stimulate or upregulate 17 existing cellular and molecular pathways that improve the capacity of cells and organisms to 18 withstand greater stress. This notion underlies much of what we know about how exercise 19 conditions the body and induces long-term adaptations. During exercise, the body is 20 exposed to various forms of stress, including thermal, metabolic, hypoxic, oxidative, and 21 mechanical stress. These stressors activate biochemical messengers, which in turn activate 22 various signaling pathways that regulate gene expression and adaptive responses. 23 Historically, antioxidant supplements, nonsteroidal anti-inflammatory drugs, and 24 cryotherapy have been favored to attenuate or counteract exercise-induced oxidative stress 25 and inflammation. However, reactive oxygen species and inflammatory mediators are key 26 signaling molecules in muscle, and such strategies may mitigate adaptations to exercise. 27 Conversely, withholding dietary carbohydrate and restricting muscle blood flow during 28 exercise may augment adaptations to exercise. In this review article, we combine, integrate, 29 and apply knowledge about the fundamental mechanisms of exercise adaptation. We also 30 critically evaluate the rationale for using interventions that target these mechanisms under 31 the overarching concept of hormesis. There is currently insufficient evidence to establish 32 whether these treatments exert dose-dependent effects on muscle adaptation. However, 33 there appears to be some dissociation between the biochemical/molecular effects and 34 functional/performance outcomes of some of these treatments. Although several of these 35 treatments influence common kinases, transcription factors and proteins, it remains to be 36 determined if these interventions complement or negate each other, and whether such 37 effects are strong enough to influence adaptations to exercise.

Bone-anchored prosthesis: Update in international developments

This symposium will provide hand-on update on the current development of the load sensors measuring the inner prosthetic loading that can strongly contribute the ever increasing demand for evidence-based clinical practice. Surgical implantations of osseointegrated fixations for bone-anchored prosthesis are developing at an unprecedented pace worldwide (e.g., Australia, UK, Sweden, US). This option is becoming accessible to a wide range of individuals with limb loss. With these new developments come new potential challenges and opportunities for all the stakeholders involved in the prosthetic care of these patients. Clearly, there is a need for those stakeholders, particularly those attending the ISPO, to be informed of the current and upcoming international developments in bone-anchored prostheses. The objectives of this symposium will be: • To present an overview of the current growth of the procedures worldwide (e.g., identification of key players, centers of activities, growth trend) with a strong focus on the introduction of the framework to evaluate the availability of the procedure at national level (e.g., number of patients treated, range of the levels of implantation, number of commercial fixations accessible), • To provide first-hand updates on the latest cutting-edge scientific and clinical developments of fixations and rehabilitations programs (e.g., Innovative design of implant, cost-effectiveness, long-terms rehabilitation outcomes for screw-type fixation, current developments in US, comparative analysis for press-fit type of implant, potential moves toward single-stage surgeries).

The cost and time effectiveness of osseointegration compared to the traditional socket prosthesis

Individuals with limb amputation fitted with conventional socket-suspended prostheses often experience socket related discomfort leading to a significant decrease in quality of life.[1-14] Most of these concerns can be overcome with osseointegration, a direct skeletal fixation method where the prosthetic componentry are directly attached to the fixation, resulting in the redundancy of the traditional socket system. There are two stages of osseointegration; Stage one, a titanium implant is inserted into the marrow space of residual limb bone and Stage two, a titanium extension is attached to the fixture. This surgical procedure is currently blooming worldwide, particularly within Queensland. Whilst providing improvements in quality of life, this new method also has potential to minimise the cost required for an amputee to ambulate during daily living. Thus, the aim of this project was to compare the differences in mean cost of services, cost of componentry and labour hours when using osseointegration compared to traditional socket-based prostheses. Data were extracted from Queensland Artificial Limb Services (QALS) database to determine cost of services, type of services and labour hours required to maintain a prosthetic limb. Five trans-femoral amputee male participants (age 46.4±10.1 yrs; height 175.4±16.3 cm; mass 83.8±14.0 kg; time since second stage 22.0± 8.1 mths) met inclusion criteria which was patient had to be more than 12 months post stage two osseointegration procedure. The socket and osseointegration prosthesis variables examined were the mean hours of labour, mean cost of services and mean cost of prosthetic componentry. Statistical analyses were conducted using an ANOVA. The results identified that there were only significant differences in the number of labour hours (p = 0.005) and cost of services (p = 0.021) when comparing the socket and osseointegration prosthetic type. These results identified that the cost of componentry were comparable between the two methods.

Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling

Macrophages play a crucial role in the maintenance and resolution of inflammation and express a number of pro- and anti-inflammatory molecules in response to stressors. Among them, the complement receptor 5a (C5aR) plays an integral role in the development of inflammatory disorders. Biliverdin and bilirubin, products of heme catabolism, exert anti-inflammatory effects and inhibit complement activation. Here, we define the effects of biliverdin on C5aR expression in macrophages and the roles of Akt and mammalian target of rapamycin (mTOR) in these responses. Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression (without altering basal expression), an effect partially blocked by rapamycin, an inhibitor of mTOR signaling. Biliverdin also reduced LPS-dependent expression of the pro-inflammatory cytokines TNF-alpha and IL-6. Collectively, these data indicate that biliverdin regulates LPS-mediated expression of C5aR via the mTOR pathway, revealing an additional mechanism underlying biliverdin's anti-inflammatory effects.

Understanding the relationship between interfragmentary movement and callus growth in fracture healing: A novel computational approach

Introduction & Aims Optimising fracture treatments requires a sound understanding of relationships between stability, callus development and healing outcomes. This has been the goal of computational modelling, but discrepancies remain between simulations and experimental results. We compared healing patterns vs fixation stiffness between a novel computational callus growth model and corresponding experimental data. Hypothesis We hypothesised that callus growth is stimulated by diffusible signals, whose production is in turn regulated by mechanical conditions at the fracture site. We proposed that introducing this scheme into computational models would better replicate the observed tissue patterns and the inverse relationship between callus size and fixation stiffness. Method Finite element models of bone healing under stiff and flexible fixation were constructed, based on the parameters of a parallel rat femoral osteotomy study. An iterative procedure was implemented, to simulate the development of callus and its mechanical regulation. Tissue changes were regulated according to published mechano-biological criteria. Predictions of healing patterns were compared between standard models, with a pre-defined domain for callus development, and a novel approach, in which periosteal callus growth is driven by a diffusible signal. Production of this signal was driven by local mechanical conditions. Finally, each model’s predictions were compared to the corresponding histological data. Results Models in which healing progressed within a prescribed callus domain predicted that greater interfragmentary movements would displace early periosteal bone formation further from the fracture. This results from artificially large distortional strains predicted near the fracture edge. While experiments showed increased hard callus size under flexible fixation, this was not reflected in the standard models. Allowing the callus to grow from a thin soft tissue layer, in response to a mechanically stimulated diffusible signal, results in a callus shape and tissue distribution closer to those observed histologically. Importantly, the callus volume increased with increasing interfragmentary movement. Conclusions A novel method to incorporate callus growth into computational models of fracture healing allowed us to successfully capture the relationship between callus size and fixation stability observed in our rat experiments. This approach expands our toolkit for understanding the influence of different fixation strategies on healing outcomes.

Habitus realisation: Negotiating identities through Chinese looks and Chinese language

The increasing linguistic and cultural diversity of our contemporary world points to the salience of maintaining and developing Heritage Language of ethnic minority groups. The mutually constitutive effect between Heritage Language learning and ethnic identity construction has been well documented in the literature. Classical social psychological work often quantitatively structures this phenomenon in a predictable linear relationship. In contrast, poststructural scholarship draws on qualitative approaches to claim the malleable and multiple dynamics behind the phenomenon. The two schools oppose but complement each other. Nevertheless, both schools struggle to capture the detailed and nuanced construction of ethnic identity through Heritage Language learning. Different from the extant research, we make an attempt to ethno-methodologically unearth the nuisances and predicaments embedded in the reflexive, subtle, and multi-layered identity constructions through nuanced, inter-nested language practices. Drawing on data from the qualitative phase of a large project, we highlight some small but powerful moments abstracted from the interview accounts of five Chinese Australian young people. Firstly, we zoom in on the life politics behind the ‘seen but unnoticed’ stereotype that looking Chinese means being able to speak Chinese. Secondly, we speculate the power relations between the speaker and the listener through the momentary and inadvertent breaches of the taken-for-granted stereotype. Next, we unveil how learning Chinese has become an accountably rational priority for these young Chinese Australians. Finally, we argue that the normalised stereotype becomes visible and hence stable when it is breached – a practical accomplishment that we term ‘habitus realisation’.

The role of innovation intermediaries in collaborative networks of small and medium-sized enterprises

The major challenge of European Union’s agricultural industry is to ensure sustainable supply of quality food that meets the demands of a rapidly growing population, changing dietary patterns, increased competition for land use, and environmental concerns. Investments in research and innovation, which facilitate integration of external knowledge in food chain operations, are crucial to undertaking such challenges. This paper addresses how SMEs successfully innovate within collaborative networks with the assistance of innovation intermediaries. In particular, we explore the roles of innovation intermediaries in knowledge acquisition, knowledge assimilation, knowledge, transformation, and knowledge exploitation in open innovation initiatives from the wine industry through the theoretical lens of absorptive capacity. Based on two case studies from the wine industry, we identified seven key activities performed by innovation intermediaries that complement SMEs’ ability to successfully leverage external sources of knowledge for innovation purposes. These activities are articulation of knowledge needs and innovation capabilities, facilitation of social interactions, establishment of complementary links, implementation of governance structures, conflict management, enhancement of transparency, and mediation of communication. Our in-depth qualitative study of two innovation intermediaries in the wine industry has several important implications that contribute to research and practice.