Green fireballs and ball lightning

This paper presents evidence of an apparent connection between ball lightning and a green fireball. On the evening of the 16th May 2006 at least three fireballs were seen by many people in the skies of Queensland, Australia. One of the fireballs was seen passing over the Great Divide about 120 km west of Brisbane, and soon after, a luminous green ball about 30 cm in diameter was seen rolling down the slope of the Great Divide. A detailed description given by a witness indicates that the phenomenon was probably a highly luminous form of ball lightning. An hypothesis presented in this paper is that the passage of the Queensland fireball meteor created an electrically conductive path between the ionosphere and ground, providing energy for the ball lightning phenomenon. A strong similarity is noted between the Queensland fireball and the Pasamonte fireball seen in New Mexico in 1933. Both meteors exhibit a twist in the tail that could be explained by hydrodynamic forces. The possibility that multiple sightings of fireballs across South East Queensland were produced owing to fragments from comet 73P Schwassmann-Wachmann 3 is discussed.

Ownership structure and business evaluation practices in family SMEs : evidence from empirical research in Italy

This paper presents early results from a pilot project which aims to investigate the relationship between proprietary structure of small and medium- sized Italian family firms and their owners’ orientation towards a “business evaluation process”. Evidence from many studies point out the importance of family business in a worldwide economic environment: in Italy 93% of the businesses are represented by family firms; 98% of them have less than 50 employees (Italian Association of Family Firms, 2004) so we judged family SMEs as a relevant field of investigation. In this study we assume a broad definition of family business as “a firm whose control (50% of shares or voting rights) is closely held by the members of the same family” (Corbetta,1995). “Business evaluation process” is intended here both as “continuous evaluation process” (which is the expression of a well developed managerial attitude) or as an “immediate valuation” (i.e. in the case of new shareholder’s entrance, share exchange among siblings, etc). We set two hypotheses to be tested in this paper: the first is “quantitative” and aims to verify whether the number of owners (independent variable) in a family firm is positively correlated to the business evaluation process. If a family firm is led by only one subject, it is more likely that personal values, culture and feelings may affect his choices more than “purely economic opportunities”; so there is less concern about monitoring economic performance or about the economic value of the firm. As the shareholders’ number increases, economic aspects in managing the firm grow in importance over the personal values and "value orientation" acquires a central role. The second hypothesis investigates if and to what extent the presence of “non- family members” among the owners affects their orientation to the business evaluation process. The “Cramer’s V” test has been used to test the hypotheses; both were not confirmed from these early results; next steps will lead to make an inferential analysis on a representative sample of the population.

A validated self-administered female pelvic floor questionnaire

Introduction and hypothesis: The aim of this study was to validate a self-administered version of the already validated interviewer-administered Australian pelvic floor questionnaire. Methods: The questionnaire was completed by 163 women attending an urogynecological clinic. Face and convergent validity was assessed. Reliability testing and comparison with the interviewer-administered version was performed in a subset of 105 patients. Responsiveness was evaluated in a subset of 73 women. Results: Missing data did not exceed 4% for any question. Cronbach’s alpha coefficients were acceptable in all domains. Kappa coefficients for the test–retest analyses varied from 0.64–1.0. Prolapse symptoms correlated significantly with the pelvic organ prolapse quantification. Urodynamics confirmed the reported symptom stress incontinence in 70%. The self and interviewer administered questionnaires demonstrated equivalence. Effect sizes ranged from 0.6 to 1.4. Conclusions: This self-administered pelvic floor questionnaire assessed pelvic floor function in a reproducible and valid fashion and due to its responsiveness, can be used for routine clinical assessment and outcome research.

The development of Lactococcus lactis as an antimicrobial agent

Non-pathogenic lactic acid bacteria are economically important Gram-positive bacteria used extensively in the food industry. Due to their “generally regarded as safe” status, certain species from the genera Lactobacillus and Lactococcus are also considered desirable as candidates for the production and secretion of recombinant proteins, particular those with therapeutic applications. The hypothesis examined by this thesis is that Lactococcus lactis can be modified to be an effective antimicrobial agent. Therefore, the aims of this thesis were to investigate the optimisation of the expression, secretion and/or activities of potential heterologous antimicrobial proteins by the model lactic acid bacterium, Lactococcus lactis subsp. cremoris MG1363. L. lactis strains were engineered to express and secrete the recombinant CyuC surface protein from Lactobacillus reuteri BR11, and a fusion protein consisting of CyuC and lysostaphin using the Sep promoter and secretion signal. CyuC has been characterised as a cystine-binding protein, but has also been demonstrated to have fibronectin binding activity. Lysostaphin is a bacteriolytic enzyme with specific activity against the Gram-positive pathogen, Staphylococcus aureus. These modified L. lactis strains were then investigated to see if they had the ability to inhibit the adhesion of S. aureus to host extracellular matrix (ECM) proteins. It was observed that the cell extracts of the L. lactis strain with the vector only (pGhost9:ISS1) was able to inhibit the adhesion of S. aureus to fibronectin, whilst the cell extracts of the L. lactis strain expressing lysostaphin was able to inhibit adhesion to keratin. Finally, this thesis has identified specific lactococcal genes that affect the secretion of lysostaphin through the use of random transposon mutagenesis. Ten mutants with higher lysostaphin activity contained insertions in four different genes encoding: (i) an uncharacterised putative transmembrane protein (llmg_0609), (ii) an enzyme catalysing the first step in peptidoglycan biosynthesis (murA2), (iii) a homolog of the oxidative defence regulator (trmA), and (iv) an uncharacterised putative enzyme involved in ubiquinone biosynthesis (llmg_2148). The higher lysostaphin activity observed in these mutants was found to be due to higher amounts of lysostaphin being secreted. The findings of this thesis contribute to the development of this organism as an antimicrobial agent and also to our understanding of L. lactis genetics.

Do Chinese traditional values matter in regulating China’s company directors? Preliminary findings from surveys in Hong Kong

This article argues that Chinese traditional values do matter in Chinese corporate governance. The object is to report on the preliminary findings of a project supported by the General Research Fund in Hong Kong (HK). Thus far the survey results from HK respondents support the authors’ hypothesis. As such, traditional Chinese values should be on the agenda of the next round of company law reforms in China

Adult human articular chondrocytes in a microcarrier-based culture system : expansion and redifferentiation

xpanding human chondrocytes in vitro while maintaining their ability to form cartilage remains a key challenge in cartilage tissue engineering. One promising approach to address this is to use microcarriers as substrates for chondrocyte expansion. While microcarriers have shown beneficial effects for expansion of animal and ectopic human chondrocytes, their utility has not been determined for freshly isolated adult human articular chondrocytes. Thus, we investigated the proliferation and subsequent chondrogenic differentiation of these clinically relevant cells on porous gelatin microcarriers and compared them to those expanded using traditional monolayers. Chondrocytes attached to microcarriers within 2 days and remained viable over 4 weeks of culture in spinner flasks. Cells on microcarriers exhibited a spread morphology and initially proliferated faster than cells in monolayer culture, however, with prolonged expansion they were less proliferative. Cells expanded for 1 month and enzymatically released from microcarriers formed cartilaginous tissue in micromass pellet cultures, which was similar to tissue formed by monolayer-expanded cells. Cells left attached to microcarriers did not exhibit chondrogenic capacity. Culture conditions, such as microcarrier material, oxygen tension, and mechanical stimulation require further investigation to facilitate the efficient expansion of clinically relevant human articular chondrocytes that maintain chondrogenic potential for cartilage regeneration applications.

A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge

The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today.

Increased Langerhan cell density and corneal nerve damage in diabetic patients : role of immune mechanisms in human diabetic neuropathy

Aim/hypothesis Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients. Methods 128 diabetic patients aged 58±1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS—4.7±0.28) and 26 control subjects aged 53±3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM). Results The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P=0.001. Furthermore, LC density (no/mm2) was significantly increased in diabetic patients (17.73±1.45) compared to control subjects (6.94±1.58), P=0.001 and there was a significant correlation with age (r=0.162, P=0.047) and severity of neuropathy (r=−0.202, P=0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r=0.414, P=0.000). Corneal nerve fibre density (P<0.001), branch density (P<0.001) and length (P<0.001) were significantly decreased whilst tortuosity (P<0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy. Conclusion Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.

Designing participation : Reconsidering agile ridesharing with evolutionary distributed design thinking

This paper explores design thinking from the perspective of designing new forms of interaction to engage people in community change initiatives. A case study of an agile ridesharing system is presented. We describe the fundamental premise of the design approach taken—deploying simple interactive prototypes for use by communities in order to test the design hypothesis, evolve the design in use and grow the community of participants. Real-time use data and feedback from participants influences our understanding of the design approach and feeds into the gradual evolution of the prototype while it continues to be used. We then reflect upon this form of evolutionary distributed design thinking. In contrast to the conventional IT wisdom of building systems to automate ride matching and fare calculation using structured forms, our initial phase of design revealed a preference for informal messaging, negotiation and caution in the sharing of specific location information.

The association between MC1R genotype and BRAF mutation status in cutaneous melanoma : findings from an Australian population

There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.

Cognitive behaviour therapy (CBT) for the treatment of co-occurring depression and substance use : current evidence and directions for future research

Issues and Approach: The high rates of co-occurring depression and substance use, and the negative impact of this on illness course and outcomes have been well established. Despite this, few clinical trials have examined the efficacy of cognitive behaviour therapy (CBT). This paper systematically reviews these clinical trials, with an aim of providing recommendations for how future research can develop a more robust evidence base for the treatment of these common comorbidities. Leading electronic databases, including PubMed (ISI) and PsychINFO (CSA), were searched for peer-reviewed journal articles using CBT for the treatment of co-occurring depression and substance use. Of the 55 articles identified, 12 met inclusion criteria and were included in the review. ---------- Key Findings: There is only a limited evidence for the effectiveness of CBT either alone or in combination with antidepressant medication for the treatment of co-occurring depression and substance use. While there is support for the efficacy of CBT over no treatment control conditions, there is little evidence that CBT is more efficacious than other psychotherapies. There is, however, consistent evidence of improvements in both depression and substance use outcomes, regardless of the type of treatment provided and there is growing evidence that that the effects of CBT are durable and increase over time during follow up. ---------- Conclusions. Rather than declaring the ‘dodo bird verdict’ that CBT and all other psychotherapies are equally efficacious, it would be more beneficial to develop more potent forms of CBT by identifying variables that mediate treatment outcomes.

Cystine-mediated oxidative defence in Lactobacillus reuteri BR11

Lactobacillus reuteri BR11 possesses an abundant cystine uptake (Cyu) ABC-transporter that was previously found to be involved in a novel mechanism of oxidative defence mediated by cystine. The current study aimed to elucidate this mechanism with a focus on the role of the co-transcribed cystathionine ã-lyase (Cgl). Growth studies of wild-type L. reuteri BR11 and mutants inactivated in cgl and the cystine-binding protein encoding gene cyuC showed that in contrast to the Cyu transporter, whose inactivation led to growth arrest in aerated cultures, Cgl is not crucial for oxidative defence. However, the role of Cgl in oxidative defence became apparent in the presence of severe oxidative damage and cysteine deprivation. Cysteine was found to be protective against oxidative stress, and the action of Cgl in both cysteine biosynthesis and degradation poses a seemingly futile pathway that deprives the intracellular cysteine pool. To further characterise the relationship between Cgl activity and cysteine and their roles in oxidative defence, enzymatic assays were performed on purified Cgl, and intracellular concentrations of cysteine, cystathionine and methionine were determined. Cgl was highly active towards cystine and cystathionine and less active towards cysteine in vitro, suggesting the main function of Cgl to be cysteine biosynthesis. Cysteine was found at high concentrations in the cell, but the levels were not significantly affected by inactivation of cgl or growth under aerobic conditions. It was concluded that both anabolic and catabolic activities of Cgl towards cysteine contribute to oxidative defence, the former by maintaining an intracellular reservoir of thiol analogous to glutathione, and the latter by producing H2S which is readily secreted, thus creating a reducing extracellular environment. The significance of the Cyu transporter to the physiology of L. reuteri BR11 prompted a phylogenetic study to determine its presence in bacteria. Orthologs of the Cyu transporter that are closest matches to the Cyu transporter are only limited to several species of Lactobacillus and Leuconostoc. Outside the Lactobacillales order, the closest matching orthologs belong to Proteobacteria, and there are more orthologs in Proteobacteria than non-Lactobacillales Firmicutes, suggesting that the Cyu transporter locus was present in the ancestor of the Proteobacteria and Firmicutes, and over evolutionary time has been lost or diverged in many Firmicutes. The clustering of the Cyu transporter locus with a gene encoding a Cgl family protein is even rarer. It was only found in L. reuteri, Lactobacillus vaginalis, Weissella paramesenteroides, the Lactobacillus casei group, and several Campylobacter sp. An accompanying phylogenetic study of L. reuteri BR11 using multi-locus sequence analysis showed that L. reuteri BR11 had diverged from more than 100 strains of L. reuteri isolated from various hosts and geographical locations. However, comparison with other Lactobacillus species supported the current classification of BR11 as L. reuteri. The most closely related species to L. reuteri is L. vaginalis or Lactobacillus antri, depending on the housekeeping gene used for analysis. The close evolutionary relationship of L. vaginalis to L. reuteri and the high degree of sequence identity between the cgl-cyuABC loci in both species suggest that the Cyu system is highly likely to perform similar functions in L. vaginalis. In search of other genes that function in oxidative defence, a number of mutants which were inactivated in genes that confer increased resistance to oxidative stress in other bacteria were constructed. The genes targeted were ahpC (peroxidase component of the alkyl hydroperoxide reductase system), tpx (thiol peroxidase), osmC (osmotically induced protein C), mntH (Mn2+/Fe2+ transporter), gshA (ã-glutamylcysteine synthetase) and msrA (methionine sulfoxide reductase). The ahpC and mntH mutants had slightly lower minimum inhibitory concentrations of organic peroxides, suggesting these genes might be involved in resistance to organic peroxides in L. reuteri. However, none of the mutants exhibited growth defects in aerated cultures, in stark contrast to the cyuC mutant. This may be due to compensatory functions of other genes, a hypothesis which cannot be tested until a robust protocol for constructing markerless multiple gene deletion mutants in L. reuteri is developed. These results highlight the importance of the Cyu transporter in oxidative defence and provide a foundation for extending the research of this system in other bacteria.

Age, muscle fatigue, and walking endurance in pre-menopausal women

Aging is associated with loss of endurance; however, aging is also associated with decreased fatigue during maximal isometric contractions. The aims of this study were to examine the relationship between age and walking endurance (WE) and maximal isometric fatigue (MIF) and to determine which metabolic/fitness components explain the expected age effects on WE and MIF. Subjects were 96 pre-menopausal women. Oxygen uptake (walking economy) was assessed during a 3-mph walk; aerobic capacity and WE by progressive treadmill test; knee extension strength by isometric contractions, MIF during a 90-s isometric plantar flexion (muscle metabolism measured by 31P MRS). Age was related to increased walking economy (low VO2, r = −0.19, P < 0.03) and muscle metabolic economy (force/ATP, 0.34, P = 0.01), and reduced MIF (−0.26, P < 0.03). However, age was associated with reduced WE (−0.28, P < 0.01). Multiple regression showed that muscle metabolic economy explained the age-related decrease in MIF (partial r for MIF and age −0.13, P = 0.35) whereas walking economy did not explain the age-related decrease in WE (partial r for WE and age −0.25, P < 0.02). Inclusion of VO2max and knee endurance strength accounted for the age-related decreased WE (partial r for WE and age = 0.03, P > 0.80). In premenopausal women, age is related to WE and MIF. In addition, these results support the hypothesis that age-related increases in metabolic economy may decrease MIF. However, decreased muscle strength and oxidative capacity are related to WE.

Human atrial beta1L-adrenoceptor but not beta3-adrenoceptor activation increases force and Ca2+ current at physiological temperature

BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.

Near infrared for non-destructive testing of articular cartilage

The concept of non-destructive testing (NDT) of materials and structures is of immense importance in engineering and medicine. Several NDT methods including electromagnetic (EM)-based e.g. X-ray and Infrared; ultrasound; and S-waves have been proposed for medical applications. This paper evaluates the viability of near infrared (NIR) spectroscopy, an EM method for rapid non-destructive evaluation of articular cartilage. Specifically, we tested the hypothesis that there is a correlation between the NIR spectrum and the physical and mechanical characteristics of articular cartilage such as thickness, stress and stiffness. Intact, visually normal cartilage-on-bone plugs from 2-3yr old bovine patellae were exposed to NIR light from a diffuse reflectance fibre-optic probe and tested mechanically to obtain their thickness, stress, and stiffness. Multivariate statistical analysis-based predictive models relating articular cartilage NIR spectra to these characterising parameters were developed. Our results show that there is a varying degree of correlation between the different parameters and the NIR spectra of the samples with R2 varying between 65 and 93%. We therefore conclude that NIR can be used to determine, nondestructively, the physical and functional characteristics of articular cartilage.