Bone tissue engineering : reconstruction of critical sized segmental bone defects in the ovine tibia

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds. Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

Engagement, persistence, progress and success as theoretically distinct aspects of business creation processes

Starting from the vantage point that explaining success at creating a venture should be the unique contribution—or at least one unique contribution—of entrepreneurship research, we argue that this success construct has not yet been adequately defined an operationalized. We thus offer suggestions for more precise conceptualization and measurement of this central construct. Rather than regarding various success proxies used in prior research as poor operationalizations of success we argue that they represent other important aspects of the venture creation process: engagement, persistence and progress. We hold that in order to attain a better understanding of venture creation these constructs also need to be theoretically defined. Further, their respective drivers need to be theorized and tested separately. We suggest theoretical definitions of each. We then develop and test hypotheses concerning how human capital, venture idea novelty and business planning has different impact on the different assessments of the process represented by engagement, persistence, progress and success. The results largely confirm the stated hypotheses, suggesting that the conceptual and empirical approach we are suggesting is a path towards improved understanding of the central entrepreneurship phenomenon of new venture creation.

Business planning, idea change, flexibility and performance: the best of both worlds?

The relationships between business planning and performance have divided the entrepreneurship research community for decades (Brinckmann et al, 2010). One side of this debate is the assumption that business plans may lock the firm in a specific direction early on, impede the firm to adapt to the changing market conditions (Dencker et al., 2009) and eventually, cause escalation of commitments by introducing rigidity (Vesper, 1993). Conversely, feedback received from the production and presentation of business plans may also lead the firm to take corrective actions. However, the mechanisms underlying the relationships between changes in business ideas, business plans and the performance of nascent firms are still largely unknown. While too many business idea changes may confuse stakeholders, exhaust the firm’s resources and hinder the undergoing legitimization process, some flexibility during the early stages of the venture may be beneficial to cope with the uncertainties surrounding new venture creation (Knight, 1921; March, 1982; Stinchcombe, 1965; Weick, 1979). Previous research has emphasized adaptability and flexibility as key success factors through effectual logic and interaction with the market (Sarasvathy, 2001; 2007) or improvisation and trial-and-error (Miner et al, 2001). However, those studies did not specifically investigate the role of business planning. Our objective is to reconcile those seemingly opposing views (flexibility versus rigidity) by undertaking a more fine-grained analysis at the relationships between business planning and changes in business ideas on a large longitudinal sample of nascent firms.

The underlying rationale for planning: do nascent and young firms do what they say they do?

Previous studies investigating the relationships between business planning and performance have led to inconclusive results (Brinckmann et al., 2010; Delmar & Shane, 2003; Frese, 2009; Gruber, 2007; Honig & Karlsson, 2004). Institutional theory argues that firms develop business plans as an answer to external and internal pressures to gain legitimization (Delmar & Shane, 2004) and funding from different stakeholders (Karlsson & Honig, 2009). Action theory suggests that planning will pave the new venture creation journey by providing milestones and a program to implement (Frese, 2009). However, studies with an institutional perspective imply that nascent firms are either conforming to or looking for the benefits of these external or internal pressures (Karlsson & Honig, 2009) while action theory assumes that the plans will be implemented (Frese, 2009). This paper attempts to (i) investigate if the intended uses of the business plans provided by nascent and young firms match their actual uses during their venture creation process and (ii) to examine how the types of uses of business plans impact the firms’ outcomes over three years.

The effect of Tenofovir on vitamin D metabolism in HIV-infected adults is dependent on sex and ethnicity

Background: Tenofovir has been associated with renal phosphate wasting, reduced bone mineral density, and higher parathyroid hormone levels. The aim of this study was to carry out a detailed comparison of the effects of tenofovir versus non-tenofovir use on calcium, phosphate and, vitamin D, parathyroid hormone (PTH), and bone mineral density. Methods: A cohort study of 56 HIV-1 infected adults at a single centre in the UK on stable antiretroviral regimes comparing biochemical and bone mineral density parameters between patients receiving either tenofovir or another nucleoside reverse transcriptase inhibitor. Principal Findings: In the unadjusted analysis, there was no significant difference between the two groups in PTH levels (tenofovir mean 5.9 pmol/L, 95% confidence intervals 5.0 to 6.8, versus non-tenofovir; 5.9, 4.9 to 6.9; p = 0.98). Patients on tenofovir had significantly reduced urinary calcium excretion (median 3.01 mmol/24 hours) compared to non-tenofovir users (4.56; p,0.0001). Stratification of the analysis by age and ethnicity revealed that non-white men but not women, on tenofovir had higher PTH levels than non-white men not on tenofovir (mean difference 3.1 pmol/L, 95% CI 5.3 to 0.9; p = 0.007). Those patients with optimal 25-hydroxyvitamin D (.75 nmol/L) on tenofovir had higher 1,25-dihydroxyvitamin D [1,25(OH)2D] (median 48 pg/mL versus 31; p = 0.012), fractional excretion of phosphate (median 26.1%, versus 14.6;p = 0.025) and lower serum phosphate (median 0.79 mmol/L versus 1.02; p = 0.040) than those not taking tenofovir. Conclusions: The effects of tenofovir on PTH levels were modified by sex and ethnicity in this cohort. Vitamin D status also modified the effects of tenofovir on serum concentrations of 1,25(OH)2D and phosphate.

The moderating role of learning on competitive advantage : longitudinal evidence from young firms

The question of how young firms reconcile the absence of well-established learning routines arising from the “liabilities of newness” with the “learning advantages of newness” has received scant attention in entrepreneurship. While older firms follow established learning routines and sometimes face problems in overcoming inertia, young firms with lower levels of inertia are better poised to explore, search and test unique avenues for their products and services. The process of learning and capability development as well as establishing uniqueness in their product offerings is an important part not only in the early stages of firm growth, but also in firm survival. Given their inexperience, for young firms, these learning processes are iterative and include contrasting learning loops that sometimes progress and at other times digress from initially perceived unique ideas. Such processes are embedded within capabilities that the firm develops and nurtures. Based on this premise and adopting a capabilities-based view, we examine how strategic networks and environmental knowledge affects uniqueness- mediated performance in young firms. We identify firms with digressive learning strategies based on their self-assessment of learning and compare them with other firms to demonstrate a differential effect on performance.

Client adaptiveness in entrepreneurship and its effect on sustained competitive advantage in project-orientated service firms

Important differences exist in how service firms operate in comparison with manufacturing firms (c.f. Johne & Storey, 1998; Tether, 2002). Despite these significant differences, not much is known whether these differences extrapolate to entrepreneurship in the services industry. This study seeks to address this gap by investigating how value creation occurs when project-oriented firms1 adopt client adaptiveness as part of their entrepreneurial posture. Specifically, we examine the effect of client adaptiveness on sustained competitive advantage. Client adaptiveness is conceptualized as the extent to which an organization engages in identifying and responding to perceived client needs and wants which reflects the service firm’s propensity to dynamically synchronize with the project/client requirements.

Vitamin D intake, sun exposure and 25-hydroxy vitamin D status in Peritoneal dialysis (PD) and Haemodialysis (HD) patients

Inadequate vitamin D levels have been linked to bone disease but more recently have been associated with wider health implications. Limited studies suggest a high prevalence of Vitamin D deficiency in dialysis patients, although evidence is lacking on whether this is due to dietary restrictions, limited mobility and time outdoors or a combination of these. The aim of this study was to assess the contributions of diet, supplements and sunlight exposure to serum Vitamin D (25(OH)D) levels in dialysis patients. Cross-sectional data were obtained from 30 PD (Mean±SD age 56.9±16.2 y; n=13 male) and 22 HD (Mean±SD age 65.4±14.0 y; n=18 male) patients between 2009 and 2010. Serum 25(OH)D was measured and oral vitamin D intake estimated through a food-frequency-questionnaire and quantifying inactive supplementation. Sunlight exposure was assessed using a validated questionnaire. Prevalence of inadequate/insufficient vitamin D differed between dialysis modality (31% and 43% insufficient (<50nmol/L); 4% and 34% deficient (<25nmol/L) in HD and PD patients respectively (p=0.002)). In HD patients, there was a significant correlation between diet plus supplemental vitamin D intake and 25(OH)D (ρ=0.84, p<0.001). Results suggest a higher frequency of 25(OH)D inadequacy/deficiency in PD compared to HD patients. No other relationships between intake, sun exposure and 25(OH)D were seen. This could reflect limitations of the study design or the importance of other factors such as age, ethnicity and sun protection as interactions in the analysis. Understanding these factors is important given Vitamin D���s emerging status as a biomarker of systemic ill health.

Volume-dependent response of precooling for intermittent-sprint exercise in the heat

Purpose: To assess the effects of pre-cooling volume on neuromuscular function and performance in free-paced intermittent-sprint exercise in the heat. Methods: Ten male, teamsport athletes completed four randomized trials involving an 85-min free-paced intermittentsprint exercise protocol in 33°C±33% relative humidity. Pre-cooling sessions included whole body (WB), head+hand (HH), head (H) and no cooling (CONT), applied for 20-min pre-exercise and 5-min mid exercise. Maximal voluntary contractions (MVC) were assessed pre- and postintervention and mid- and post-exercise. Exercise performance was assessed with sprint times, % decline and distances covered during free-paced bouts. Measures of core(Tc) and skin (Tsk) temperatures, heart rate, perceptual exertion and thermal stress were monitored throughout. Venous and capillary blood was analyzed for metabolite, muscle damage and inflammatory markers. Results: WB pre-cooling facilitated the maintenance of sprint times during the exercise protocol with reduced % decline (P=0.04). Mean and total hard running distances increased with pre cooling 12% compared to CONT (P<0.05), specifically, WB was 6-7% greater than HH (P=0.02) and H (P=0.001) respectively. No change was evident in mean voluntary or evoked force pre- to post-exercise with WB and HH cooling (P>0.05). WB and HH cooling reduced Tc by 0.1-0.3°C compared to other conditions (P<0.05). WB Tsk was suppressed for the entire session(P=0.001). HR responses following WB cooling were reduced(P=0.05; d=1.07) compared to CONT conditions during exercise. Conclusion: A relationship between pre-cooling volume and exercise performance seems apparent, as larger surface area coverage augmented subsequent free-paced exercise capacity, in conjunction with greater suppression of physiological load. Maintenance of MVC with pre-cooling, despite increased work output suggests the role of centrally-mediated mechanisms in exercise pacing regulation and subsequent performance.

Duration-dependant response of mixed-method pre-cooling for intermittent-sprint exercise in the heat

This study examined the effects of pre-cooling duration on performance and neuromuscular function for self-paced intermittent-sprint shuttle running in the heat. Eight male, team-sport athletes completed two 35-min bouts of intermittent-sprint shuttle running separated by a 15-min recovery on three separate occasions (33°C, 34% relative humidity). Mixed-method pre-cooling was completed for 20 min (COOL20), 10-min (COOL10) or no cooling (CONT) and reapplied for 5-min mid-exercise. Performance was assessed via sprint times, percentage decline and shuttle-running distance covered. Maximal voluntary contractions (MVC), voluntary activation (VA) and evoked twitch properties were recorded pre- and post-intervention and mid- and post-exercise. Core temperature (T c), skin temperature, heart rate, capillary blood metabolites, sweat losses, perceptual exertion and thermal stress were monitored throughout. Venous blood draws pre- and post-exercise were analyzed for muscle damage and inflammation markers. Shuttle-running distances covered were increased 5.2 ± 3.3% following COOL20 (P < 0.05), with no differences observed between COOL10 and CONT (P > 0.05). COOL20 aided in the maintenance of mid- and post-exercise MVC (P < 0.05; d > 0.80), despite no conditional differences in VA (P > 0.05). Pre-exercise T c was reduced by 0.15 ± 0.13°C with COOL20 (P < 0.05; d > 1.10), and remained lower throughout both COOL20 and COOL10 compared to CONT (P < 0.05; d > 0.80). Pre-cooling reduced sweat losses by 0.4 ± 0.3 kg (P < 0.02; d > 1.15), with COOL20 0.2 ± 0.4 kg less than COOL10 (P = 0.19; d = 1.01). Increased pre-cooling duration lowered physiological demands during exercise heat stress and facilitated the maintenance of self-paced intermittent-sprint performance in the heat. Importantly, the dose-response interaction of pre-cooling and sustained neuromuscular responses may explain the improved exercise performance in hot conditions.

Collective dynamics and control of a 3-D small-world network with time delays

The paper presents a detailed analysis on the collective dynamics and delayed state feedback control of a three-dimensional delayed small-world network. The trivial equilibrium of the model is first investigated, showing that the uncontrolled model exhibits complicated unbounded behavior. Then three control strategies, namely a position feedback control, a velocity feedback control, and a hybrid control combined velocity with acceleration feedback, are then introduced to stabilize this unstable system. It is shown in these three control schemes that only the hybrid control can easily stabilize the 3-D network system. And with properly chosen delay and gain in the delayed feedback path, the hybrid controlled model may have stable equilibrium, or periodic solutions resulting from the Hopf bifurcation, or complex stranger attractor from the period-doubling bifurcation. Moreover, the direction of Hopf bifurcation and stability of the bifurcation periodic solutions are analyzed. The results are further extended to any "d" dimensional network. It shows that to stabilize a "d" dimensional delayed small-world network, at least a "d – 1" order completed differential feedback is needed. This work provides a constructive suggestion for the high dimensional delayed systems.