A comparative study of the proliferation and osteogenic differentiation of human periodontal ligament cells cultured on β-TCP ceramics and demineralized bone matrix with or without osteogenic inducers in vitro

The repair of bone defects that result from periodontal diseases remains a clinical challenge for periodontal therapy. β-tricalcium phosphate (β-TCP) ceramics are biodegradable inorganic bone substitutes with inorganic components that are similar to those of bone. Demineralized bone matrix (DBM) is an acid-extracted organic matrix derived from bone sources that consists of the collagen and matrix proteins of bone. A few studies have documented the effects of DBM on the proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The aim of the present study was to investigate the effects of inorganic and organic elements of bone on the proliferation and osteogenic differentiation of hPDLCs using three-dimensional porous β-TCP ceramics and DBM with or without osteogenic inducers. Primary hPDLCs were isolated from human periodontal ligaments. The proliferation of the hPDLCs on the scaffolds in the growth culture medium was examined using a Cell‑Counting kit‑8 (CCK-8) and scanning electron microscopy (SEM). Alkaline phosphatase (ALP) activity and the osteogenic differentiation of the hPDLCs cultured on the β-TCP ceramics and DBM were examined in both the growth culture medium and osteogenic culture medium. Specific osteogenic differentiation markers were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SEM images revealed that the cells on the β-TCP were spindle-shaped and much more spread out compared with the cells on the DBM surfaces. There were no significant differences observed in cell proliferation between the β-TCP ceramics and the DBM scaffolds. Compared with the cells that were cultured on β-TCP ceramics, the ALP activity, as well as the Runx2 and osteocalcin (OCN) mRNA levels in the hPDLCs cultured on DBM were significantly enhanced both in the growth culture medium and the osteogenic culture medium. The organic elements of bone may exhibit greater osteogenic differentiation effects on hPDLCs than the inorganic elements.

Design and experimental testing of air slab caps which convert commercial electron diodes into dual purpose, correction-free diodes for small field dosimetry

Purpose Two diodes which do not require correction factors for small field relative output measurements are designed and validated using experimental methodology. This was achieved by adding an air layer above the active volume of the diode detectors, which canceled out the increase in response of the diodes in small fields relative to standard field sizes. Methods Due to the increased density of silicon and other components within a diode, additional electrons are created. In very small fields, a very small air gap acts as an effective filter of electrons with a high angle of incidence. The aim was to design a diode that balanced these perturbations to give a response similar to a water-only geometry. Three thicknesses of air were placed at the proximal end of a PTW 60017 electron diode (PTWe) using an adjustable “air cap”. A set of output ratios (ORfclin Det ) for square field sizes of side length down to 5 mm was measured using each air thickness and compared to ORfclin Det measured using an IBA stereotactic field diode (SFD). k fclin, f msr Qclin,Qmsr was transferred from the SFD to the PTWe diode and plotted as a function of air gap thickness for each field size. This enabled the optimal air gap thickness to be obtained by observing which thickness of air was required such that k fclin, f msr Qclin,Qmsr was equal to 1.00 at all field sizes. A similar procedure was used to find the optimal air thickness required to make a modified Sun Nuclear EDGE detector (EDGEe) which s “correction-free” in small field relative dosimetry. In addition, the feasibility of experimentally transferring k fclin, f msr Qclin,Qmsr values from the SFD to unknown diodes was tested by comparing the experimentally transferred k fclin, f msr Qclin,Qmsr values for unmodified PTWe and EDGEe diodes to Monte Carlo simulated values. Results 1.0 mm of air was required to make the PTWe diode correction-free. This modified diode (PTWeair) produced output factors equivalent to those in water at all field sizes (5–50 mm). The optimal air thickness required for the EDGEe diode was found to be 0.6 mm. The modified diode (EDGEeair) produced output factors equivalent to those in water, except at field sizes of 8 and 10 mm where it measured approximately 2% greater than the relative dose to water. The experimentally calculated k fclin, f msr Qclin,Qmsr for both the PTWe and the EDGEe diodes (without air) matched Monte Carlo simulated results, thus proving that it is feasible to transfer k fclin, f msr Qclin,Qmsr from one commercially available detector to another using experimental methods and the recommended experimental setup. Conclusions It is possible to create a diode which does not require corrections for small field output factor measurements. This has been performed and verified experimentally. The ability of a detector to be “correction-free” depends strongly on its design and composition. A nonwater-equivalent detector can only be “correction-free” if competing perturbations of the beam cancel out at all field sizes. This should not be confused with true water equivalency of a detector.

Knowledge management challenges in small-and medium-sized enterprises

Background & Research Focus Managing knowledge for innovation and organisational benefit has been extensively investigated in studies of large firms (Smith, Collins & Clark, 2005; Zucker, et al., 2007) and to a large extent there is limited research into studies of small- and medium- sized enterprises (SMEs). There are some investigations in knowledge management research on SMEs, but what remains to be seen in particular is the question of where are the potential challenges for managing knowledge more effectively within these firms? Effective knowledge management (KM) processes and systems lead to improved performance in pursuing distinct capabilities that contribute to firm-level innovation (Nassim 2009; Zucker et al. 2007; Verona and Ravasi 2003). Managing internal and external knowledge in a way that links it closely to the innovation process can assist the creation and implementation of new products and services. KM is particularly important in knowledge intensive firms where the knowledge requirements are highly specialized, diverse and often emergent. However, to a large extent the KM processes of small firms that are often the source of new knowledge and an important element of the value networks of larger companies have not been closely studied. To address this gap which is of increasing importance with the growing number of small firms, we need to further investigate knowledge management processes and the ways that firms find, capture, apply and integrate knowledge from multiple sources for their innovation process. This study builds on the previous literature and applies existing frameworks and takes the process and activity view of knowledge management as a starting point of departure (see among others Kraaijenbrink, Wijnhoven & Groen, 2007; Enberg, Lindkvist, & Tell, 2006; Lu, Wang & Mao, 2007). In this paper, it is attempted to develop a better understanding of the challenges of knowledge management within the innovation process in small knowledge-oriented firms. The paper aims to explore knowledge management processes and practices in firms that are engaged in the new product/service development programs. Consistent with the exploratory character of the study, the research question is: How is knowledge integrated, sourced and recombined from internal and external sources for innovation and new product development? Research Method The research took an exploratory case study approach and developed a theoretical framework to investigate the knowledge situation of knowledge-intensive firms. Equipped with the conceptual foundation, the research adopted a multiple case study method investigating four diverse Australian knowledge-intensive firms from IT, biotechnology, nanotechnology and biochemistry industries. The multiple case study method allowed us to document in some depth the knowledge management experience of the theses firms. Case study data were collected through a review of company published data and semi-structured interviews with managers using an interview guide to ensure uniform coverage of the research themes. This interview guide was developed following development of the framework and a review of the methodologies and issues covered by similar studies in other countries and used some questions common to these studies. It was framed to gather data around knowledge management activity within the business, focusing on the identification, acquisition and utilisation of knowledge, but collecting a range of information about subject as well. The focus of the case studies was on the use of external and internal knowledge to support their knowledge intensive products and services. Key Findings Firstly a conceptual and strategic knowledge management framework has been developed. The knowledge determinants are related to the nature of knowledge, organisational context, and mechanism of the linkages between internal and external knowledge. Overall, a number of key observations derived from this study, which demonstrated the challenges of managing knowledge and how important KM is as a management tool for innovation process in knowledge-oriented firms. To summarise, findings suggest that knowledge management process in these firms is very much project focused and not embedded within the overall organisational routines and mainly based on ad hoc and informal processes. Our findings highlighted lack of formal knowledge management process within our sampled firms. This point to the need for more specialised capabilities in knowledge management for these firms. We observed a need for an effective knowledge transfer support system which is required to facilitate knowledge sharing and particularly capturing and transferring tacit knowledge from one team members to another. In sum, our findings indicate that building effective and adaptive IT systems to manage and share knowledge in the firm is one of the biggest challenges for these small firms. Also, there is little explicit strategy in small knowledge-intensive firms that is targeted at systematic KM either at the strategic or operational level. Therefore, a strategic approach to managing knowledge for innovation as well as leadership and management are essential to achieving effective KM. In particular, research findings demonstrate that gathering tacit knowledge, internal and external to the organization, and applying processes to ensure the availability of knowledge for innovation teams, drives down the risks and cost of innovation. KM activities and tools, such as KM systems, environmental scanning, benchmarking, intranets, firm-wide databases and communities of practice to acquire knowledge and to make it accessible, were elements of KM. Practical Implications The case study method that used in this study provides practical insight into the knowledge management process within Australian knowledge-intensive firms. It also provides useful lessons which can be used by other firms in managing the knowledge more effectively in the innovation process. The findings would be helpful for small firms that may be searching for a practical method for managing and integrating their specialised knowledge. Using the results of this exploratory study and to address the challenges of knowledge management, this study proposes five practices that are discussed in the paper for managing knowledge more efficiently to improve innovation: (1) Knowledge-based firms must be strategic in knowledge management processes for innovation, (2) Leadership and management should encourage various practices for knowledge management, (3) Capturing and sharing tacit knowledge is critical and should be managed, (4)Team knowledge integration practices should be developed, (5) Knowledge management and integration through communication networks, and technology systems should be encouraged and strengthen. In sum, the main managerial contribution of the paper is the recognition of knowledge determinants and processes, and their effects on the effective knowledge management within firm. This may serve as a useful benchmark in the strategic planning of the firm as it utilises new and specialised knowledge.

Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium

We characterised the effects of selective oestrogen receptor modulators (SERM) in explant cultures of human endometrium tissue. Endometrium tissues were cultured for 24 h in Millicell-CM culture inserts in serum-free medium in the presence of vehicle,17 beta-estradiol (17 beta-E2,1 nM), oestrogen receptor (ER) antagonist ICI 164.384 (40 nM), and 4-OH-tamoxifen (40 nM), raloxifene (4 nM), lasofoxifene (4 nM)and acolbifene (4 nM). Protein expression of ER alpha, ER beta 1 and Ki-67 were evaluated by immunohistochemistry (IHC). The proliferative fraction was assessed by counting the number of Ki-67 positive cells. Nuclear staining of ER( and ER(1 was observed in the glandular epithelium and stroma of pre- and postmenopausal endometrium. ER(1 protein was also localized in the endothelial cells of blood vessels. Treating premenopausal endometrium tissue with 17 beta-E2 increased the fraction of Ki-67 positive cells (p < 0.001) by 55% in glands compared to the control. Raloxifene (4 nM) increased (p < 0.05) the Ki-67 positive fraction. All other SERMS did not affect proliferation in this model. Treating postmenopausal endometrium with 17(-E2 increased (p < 0.001) the fraction of Ki-67 positive cells by 250% in glands compared to the control. A similar effect was also seen for 4-OH-tamoxifen, whereas the rest of SERMs did not stimulate proliferation. We demonstrated that oestradiol increases the fraction of proliferating cells in short term explant cultures of postmenopausal endometrium. In addition, we were able to reveal the agonistic properties of 4-OH-tamoxifen and confirm that raloxifene and next-generation SERMs acolbifene and lasofoxifene were neutral on the human postmenopausal endometrium. (C) 2008 Elsevier Ltd. All rights reserved.

On the (ir)relevance of rates of return measures of economic performance to small boats

A common measure of the economic performance of different fleet segments in fisheries is the rate of return on capital. However, in the English Channel (UK), observed changes in the fleet structure are at odds with expectations given the observed rates of return on capital. This disjunction between expected and observed behaviour raises the question as to the appropriateness of rate of return on capital as a measure of economic performance for small boats whose main input is often non-wage labour. In this paper, an alternative performance indicator is developed based on returns on owner-operator labour. This indicator appears to be of more relevance to small scale boats than the traditional returns on capital, and a better indicator of the direction of adjustment in the fishery.

How small business advisory program delivery methods (collective learning, tailored, and practice-based approaches) affect learning and innovation

Past studies relate small business advisory program effectiveness to advisory characteristics such as advisory intensity and scope. We contribute to existing literature by seeking to identify the impact of different advisory program methods of delivery on learning and subsequent firm innovation behavior. Our research is based on a survey of 257 Australian firms completing small business advisory programs in the three years preceding the research. We explore the range of small business advisory program delivery methods in which our surveyed firms participated and, with reference to the literature on organizational learning and innovation, we analyze predictors of firms' learning ability and innovativeness based on the identified delivery methods. First, we found that business advisory programs that involved high levels of collective learning and tailored approaches enhanced firms' perceptions of their learning of critical skills or capabilities. We also found that small business advisory programs that were delivered by using practice-based approaches enhanced firms' subsequent organizational innovation. We verified this finding by testing whether firms that have participated in small business advisory services subsequently demonstrate improved behavior in terms of organizational innovativeness, when compared with matched firms that have not participated in an advisory program.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Second ESMO consensus conference on lung cancer : pathology and molecular biomarkers for non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with nonsmall- cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.

Shifting from production to purpose : facilitating design-led change in a small family-owned enterprise

This research was embedded as a Design-led Innovation catalyst within a family-owned small business, to explore the application of a design program to achieve organizational change. Based on the findings two new models for increasing design integration within an organisation were proposed, establishing a range of pre-requisites needed for a firm to progress. Struggling firms may leverage their use of design and strategy by embedding a catalyst in a new cross-disciplinary role providing the necessary internal assistance. The study demonstrated that even non-design or strategy-inclined family-owned SMEs could benefit from embarking on a design-led journey to boost their competitive preparedness.

Displaced granulosa cells in peritoneal washings : a rare diagnostic pitfall

Developing follicles and follicular cysts in the ovary are lined by granulosa cells. Approximately the size of histiocytes, non-neoplastic granulosa cells have scant granular to foamy cytoplasm and mildly atypical hyperchromatic nuclei, which may be mitotically active. 1 Displaced granulosa cells, derived from normal follicles and introduced into ovarian vascular channels, ovarian stroma and the fallopian tube, have been reported to cause diagnostic difficulty in histol- ogy, as they may mimic small cell carcinoma or other metastatic carcinomas. 2–4 The cells are thought to be displaced artefactually due to surgical trauma or during sectioning in the laboratory or during ovulation...

Very small field dosimetry

This thesis investigated in detail the physics of small X-ray fields used in radiotherapy treatments. Because of this work, the ability to accurately measure dose from these very small X-ray fields has been improved in several ways. These include scientifically quantifying when highly accurate measurements are required by introducing the concept of a very small field, and by the invention of a new detector that responds the same in very small fields as in normal fields.

Small and medium enterprises using software as a service : exploring the different roles of intermediaries

Software as a Service (SaaS) can provide significant benefits to small and medium enterprises (SMEs) due to advantages like ease of access, 7*24 availability, and utility pricing. However, underlying the SaaS delivery model is often the assumption that SMEs will directly interact with the SaaS vendor and use a self-service approach. In practice, we see the rise of SaaS intermediaries who can support SMEs with sourcing and leveraging SaaS. This paper reports on the roles of intermediaries and how they support SMEs with using SaaS. We conducted an empirical study of two SaaS intermediaries and analysed their business models, in particular their value propositions. We identified orientation (technology or customer) and alignment (operational or strategic) as themes for understanding their roles. The contributions of this paper include: (1) the identification and description of SaaS intermediaries for SMEs based on an empirical study and (2) understanding the different roles of SaaS intermediaries, in particular a more basic role based on technology orientation and operational alignment and a more value adding role based on customer orientation and strategic alignment. We propose that SaaS intermediaries can address SaaS adoption and implementation challenges of SMEs by playing a basic role and can also aim to support SMEs in creating business value with SaaS based solutions by playing an added value role.

Using qualitative mixed methods to study small health care organizations while maximising trustworthiness and authenticity

Background The primary health care sector delivers the majority of health care in western countries through small, community-based organizations. However, research into these healthcare organizations is limited by the time constraints and pressure facing them, and the concern by staff that research is peripheral to their work. We developed Q-RARA—Qualitative Rapid Appraisal, Rigorous Analysis—to study small, primary health care organizations in a way that is efficient, acceptable to participants and methodologically rigorous. Methods Q-RARA comprises a site visit, semi-structured interviews, structured and unstructured observations, photographs, floor plans, and social scanning data. Data were collected over the course of one day per site and the qualitative analysis was integrated and iterative. Results We found Q-RARA to be acceptable to participants and effective in collecting data on organizational function in multiple sites without disrupting the practice, while maintaining a balance between speed and trustworthiness. Conclusions The Q-RARA approach is capable of providing a richly textured, rigorous understanding of the processes of the primary care practice while also allowing researchers to develop an organizational perspective. For these reasons the approach is recommended for use in small-scale organizations both within and outside the primary health care sector.