Shift in disease burden from communicable to non-communicable diseases: Aiming to achieve Universal Health Coverage in Nepal

A major barrier to accessing healthcare services is spending, and the extended time that non-communicable diseases require treatment for means that many people around the world do not have proper access to care. Saval Khanal from Sankalpa Foundation, Nepal, Lennert Veerman and Samantha Hollingworth from the University of Queensland and Lisa Nissen from Queensland University of Technology lay out the results of their study and establish a method to forecast medicine use in Nepal.

A conditionally linearized Monte Carlo filter in non-linear structural dynamics

State and parameter estimations of non-linear dynamical systems, based on incomplete and noisy measurements, are considered using Monte Carlo simulations. Given the measurements. the proposed method obtains the marginalized posterior distribution of an appropriately chosen (ideally small) subset of the state vector using a particle filter. Samples (particles) of the marginalized states are then used to construct a family of conditionally linearized system of equations and thus obtain the posterior distribution of the states using a bank of Kalman filters. Discrete process equations for the marginalized states are derived through truncated Ito-Taylor expansions. Increased analyticity and reduced dispersion of weights computed over a smaller sample space of marginalized states are the key features of the filter that help achieve smaller sample variance of the estimates. Numerical illustrations are provided for state/parameter estimations of a Duffing oscillator and a 3-DOF non-linear oscillator. Performance of the filter in parameter estimation is also assessed using measurements obtained through experiments on simple models in the laboratory. Despite an added computational cost, the results verify that the proposed filter generally produces estimates with lower sample variance over the standard sequential importance sampling (SIS) filter.

Embedding Of Non-Simple Lie-Groups, Coupling-Constant Relations And Non-Uniqueness Of Models Of Unification

A general derivation of the coupling constant relations which result on embedding a non-simple group like SU L (2) @ U(1) in a larger simple group (or graded Lie group) is given. It is shown that such relations depend only on the requirement (i) that the multiplet of vector fields form an irreducible representation of the unifying algebra and (ii) the transformation properties of the fermions under SU L (2). This point is illustrated in two ways, one by constructing two different unification groups containing the same fermions and therefore have same Weinberg angle; the other by putting different SU L (2) structures on the same fermions and consequently have different Weinberg angles. In particular the value sin~0=3/8 is characteristic of the sequential doublet models or models which invoke a large number of additional leptons like E 6, while addition of extra charged fermion singlets can reduce the value of sin ~ 0 to 1/4. We point out that at the present time the models of grand unification are far from unique.

Non-linear flapping vibrations of rotating blades

The non-linear equations of motion of a rotating blade undergoing extensional and flapwise bending vibration are derived, including non-linearities up to O (ε3). The strain-displacement relationship derived is compared with expressions derived by earlier investigators and the errors and the approximations made in some of those are brought out. The equations of motion are solved under the inextensionality condition to obtain the influence of the amplitude on the fundamental flapwise natural frequency of the rotating blade. It is found that large finite amplitudes have a softening effect on the flapwise frequency and that this influence becomes stronger at higher speeds of rotation.

A taxonomic approach to understanding managerial ethical decision making approaches of clinically and non-clinically trained healthcare managers in Australia

Objective To understand differences in the managerial ethical decision-making styles of Australian healthcare managers through the exploratory use of the Managerial Ethical Profiles (MEP) Scale. Background Healthcare managers (doctors, nurses, allied health practitioners and non-clinically trained professionals) are faced with a raft of variables when making decisions within the workplace. In the absence of clear protocols and policies healthcare managers rely on a range of personal experiences, personal ethical philosophies, personal factors and organizational factors to arrive at a decision. Understanding the dominant approaches to managerial ethical decision-making, particularly for clinically trained healthcare managers, is a fundamental step in both increasing awareness of the importance of how managers make decisions, but also as a basis for ongoing development of healthcare managers. Design Cross-sectional. Methods The study adopts a taxonomic approach that simultaneously considers multiple ethical factors that potentially influence managerial ethical decision-making. These factors are used as inputs into cluster analysis to identify distinct patterns of influence on managerial ethical decision-making. Results Data analysis from the participants (n=441) showed a similar spread of the five managerial ethical profiles (Knights, Guardian Angels, Duty Followers, Defenders and Chameleons) across clinically trained and non-clinically trained healthcare managers. There was no substantial statistical difference between the two manager types (clinical and non-clinical) across the five profiles. Conclusion This paper demonstrated that managers that came from clinical backgrounds have similar ethical decision-making profiles to non-clinically trained managers. This is an important finding in terms of manager development and how organisations understand the various approaches of managerial decision-making across the different ethical profiles.

Molecular and epidemiological aspects of Streptococcus pyogenes disease in Finland: Severe infections and bacterial, non-necrotizing cellulitis

Streptococcus pyogenes (group A streptococcus) is an important human pathogen, causing a wide array of infections ranging in severity. The majority of S. pyogenes infections are mild upper respiratory tract or skin infections. Severe, invasive infections, such as bacteraemia, are relatively rare, but constitute a major global burden with a high mortality. Certain streptococcal types are associated with a more severe disease and higher mortality. Bacterial, non-necrotizing cellulitis and erysipelas are localised infections of the skin, and although they are usually not life-threatening, they have a tendency to recur and therefore cause substantial morbidity. Despite several efforts aimed at developing an effective and safe vaccine against S. pyogenes infections, no vaccine is yet available. In this study, the epidemiology of invasive S. pyogenes infections in Finland was described over a decade of national, population-based surveillance. Recent trends in incidence, outcome and bacterial types were investigated. The beta-haemolytic streptococci causing cellulitis and erysipelas infections in Finland were studied in a case-control study. Bacterial isolates were characterised using both conventional and molecular typing methods, such as the emm typing, which is the most widely used typing method for beta-haemolytic streptococci. The incidence of invasive S. pyogenes disease has had an increasing trend during the past ten years in Finland, especially from 2006 onwards. Age- and sex-specific differences in the incidence rate were identified, with men having a higher incidence than women, especially among persons aged 45-64 years. In contrast, more infections occurred in women aged 25-34 years than men. Seasonal patterns with occasional peaks during the midsummer and midwinter were observed. Differences in the predisposing factors and underlying conditions of patients may contribute to these distinctions. Case fatality associated with invasive S. pyogenes infections peaked in 2005 (12%) but remained at a reasonably low level (8% overall during 2004-2007) compared to that of other developed countries (mostly exceeding 10%). Changes in the prevalent emm types were associated with the observed increases in incidence and case fatality. In the case-control study, acute bacterial non-necrotizing cellulitis was caused predominantly by Streptococcus dysgalactiae subsp. equisimilis, instead of S. pyogenes. The recurrent nature of cellulitis became evident. This study adds to our understanding of S. pyogenes infections in Finland and provides a basis for comparison to other countries and future trends. emm type surveillance and outcome analyses remain important for detecting such changes in type distribution that might lead to increases in incidence and case fatality. Bacterial characterisation serves as a basis for disease pathogenesis studies and vaccine development.

Fair value accounting for non-current assets and audit fees: Evidence from Australian companies

We investigate the association between asset revaluations of non-current assets and audit fees, using a sample of ASX 300 companies from the years 2003–2007.We report that there is a significant increase in the audit fees paid when non-financial assets (PPEs, investment properties and intangible assets) are measured at fair values. Moreover, we provide evidence that an independent valuer or appraiser significantly weakens the positive association between asset revaluations and audit fees. Furthermore, companies whose noncurrent assets are revalued upwards and those that revalue their non-current assets upwards every year have significantly higher audit fees. Additional tests provide empirical evidence that the strength of corporate governance has a moderating effect on the level of audit fees. This study contributes to the ongoing debate on the role of fair value accounting. The findings suggest agency costs associated with fair value estimates may offset the benefits from the use of fair value accounting.

Thermodynamic and kinetic studies on saccharide binding to soya-bean agglutinin.

The fluorescence of N-dansylgalactosamine [N-(5-dimethylaminonaphthalene-1-sulphonyl)galactosamine] was enhanced 11-fold with a 25 nm blue-shift in the emission maximum upon binding to soya-bean agglutinin (SBA). This change was used to determine the association constants and thermodynamic parameters for this interaction. The association constant of 1.51 X 10(6) M-1 at 20 degrees C indicated a very strong binding, which is mainly due to a relatively small entropy value, as revealed by the thermodynamic parameters: delta G = -34.7 kJ X mol-1, delta H = -37.9 kJ X mol-1 and delta S = -10.9 J X mol-1 X K-1. The specific binding of this sugar to SBA shows that the lectin can accommodate a large hydrophobic substituent on the C-2 of galactose. Binding of non-fluorescent ligands, studied by monitoring the fluorescence changes when they are added to a mixture of SBA and N-dansylgalactosamine, indicates that a hydrophobic substituent at the anomeric position increases the affinity of the interaction. The C-6 hydroxy group also stabilizes the binding considerably. Kinetics of binding of N-dansylgalactosamine to SBA studied by stopped-flow spectrofluorimetry are consistent with a single-step mechanism and yielded k+1 = 2.4 X 10(5) M-1 X s-1 and k-1 = 0.2 s-1 at 20 degrees C. The activation parameters indicate an enthalpicly controlled association process.

Discussion of enthalpy, entropy and free energy of formation of GaN

Presented in this letter is a critical discussion of a recent paper on experimental investigation of the enthalpy, entropy and free energy of formation of gallium nitride (GaN) published in this journal [T.J. Peshek, J.C. Angus, K. Kash, J. Cryst. Growth 311 (2008) 185-189]. It is shown that the experimental technique employed detects neither the equilibrium partial pressure of N-2 corresponding to the equilibrium between Ga and GaN at fixed temperatures nor the equilibrium temperature at constant pressure of N-2. The results of Peshek et al. are discussed in the light of other information on the Gibbs energy of formation available in the literature. Entropy of GaN is derived from heat-capacity measurements. Based on a critical analysis of all thermodynamic information now available, a set of optimized parameters is identified and a table of thermodynamic data for GaN developed from 298.15 to 1400 K.

Genetic influences on handedness: data from 25,732 Australian and Dutch twin families

Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.

Long-term Ingham and Mackay farming system experiments: comparisons between permanent non-tilled beds and re-formed beds

Experiments involving row spacing and tillage, originally established in Mackay and Ingham in 2001, were planted to a second cycle of sugarcane in 2006 following a soybean break. Despite large yield differences, economic analysis indicated that there would be little difference in gross margins because of the much higher costs of the tilled system. It is concluded that without GPS guidance, as was the case with these experiments, cane yields are likely to be reduced with no tillage but these problems may well be overcome by implementing minimum strategic tillage to remove compaction from the planting row.

Adenoviral gene therapy for non-small cell lung cancer

Adenoviral gene therapy is an experimental approach to cancer refractory to standard cancer therapies. Adenoviruses can be utilized as vectors to deliver therapeutic transgenes into cancer cells, while gene therapy with oncolytic adenoviruses exploits the lytic potential of viruses to kill tumor cells. Although adenoviruses demonstrate several advantages over other vectors - such as the unparalleled transduction efficacy and natural tropism to a wide range of tissues - the gene transfer efficacy to cancer cells has been limited, consequently restricting the therapeutic effect. There are, however, several approaches to circumvent this problem. We utilized different modified adenoviruses to obtain information on adenovirus tropism towards non-small cell lung cancer (NSCLC) cells. To enhance therapeutic outcome, oncolytic adenoviruses were evaluated. Further, to enhance gene delivery to tumors, we used mesenchymal stem cells (MSCs) as carriers. To improve adenovirus specificity, we investigated whether widely used cyclooxygenase 2 (Cox-2) promoter is induced by adenovirus infection in nontarget cells and whether selectivity can be retained by the 3 untranslated region (UTR) AU-rich elements. In addition, we investigated whether switching adenovirus fiber can retain gene delivery in the presence of neutralizing antibodies. Our results show that adenoviruses, whose capsids were modified with arginine-glycine-aspartatic acid (RGD-4C), the serotype 3 knob, or polylysins displayed enhanced gene transfer into NSCLC cell lines and fresh clinical specimens from patients. The therapeutic efficacy was further improved by using respective oncolytic adenoviruses with isogenic 24bp deletion in the E1A gene. Cox-2 promoter was also shown to be induced in normal and tumor cells following adenovirus infection, but utilization of 3 UTR elements can increase the tumor specificity of the promoter. Further, the results suggested that use of MSCs could enhance the bioavailability and delivery of adenoviruses into human tumors, although cells had no tumor tropism per se. Finally, we demonstrated that changing adenovirus fiber can allow virus to escape from existing neutralizing antibodies when delivered systemically. In conclusion, these results reveal that adenovirus gene transfer and specificity can be increased by using modified adenoviruses and MSCs as carriers, and fiber modifications simultaneously decrease the effect of neutralizing antibodies. This promising data suggest that these approaches could translate into clinical testing in patients with NSCLC refractory to current modalities.

Resistance Mechanisms of Non-Hodgkin Lymphomas against Rituximab Treatment

Rituximab, a monoclonal antibody against B-cell specific CD20 antigen, is used for the treatment of non-Hodgkin lymphomas (NHL) and chronic lymphatic leukemia. In combination with chemotherapeutics rituximab has remarkably improved the outcome of NHL patients, but a vast variation in the lengths of remissions remains and the outcome of individual patients is difficult to predict. This thesis has searched for an explanation for this by studying the effector mechanisms of rituximab and by comparing gene expression in lymphoma tissue samples of patients with long- and short-term survival. This work demonstrated that activation of complement (C) system is in vitro more efficient effector mechanism of rituximab than cellular mechanisms or apoptosis. Activation of the C system was also shown in vivo during rituximab treatment. However, intravenously administered rituximab could not enter the cerebrospinal fluid, and neither C activation nor removal of lymphoma cells was observed in central nervous system. In vitro cytotoxicity assays showed that rituximab-induced cell killing could be markedly improved with simultaneous neutralization of the C regulatory proteins CD46 (Membrane cofactor protein), CD55 (Decay-accelerating factor), and CD59 (protectin). In a retrospective study of follicular lymphoma (FL) patients, low lymphoma tissue mRNA expressions of CD59 and CD55 were associated with a good prognosis and in a progressive flow cytometry study high expression of CD20 relative to CD55 was correlated to a longer progression free survival. Gene expression profile analysis revealed that expression of certain often cell cycle, signal transduction or immune response related genes correlate with clinical outcome of FL patients. Emphasizing the role of tumor microenvironment the best differentiating genes Smad1 and EphA1 were demonstrated to be mainly expressed in the non-malignant cells of tumors. In conclusion, this thesis shows that activation of the C system is a clinically important effector mechanism of rituximab and that microenvironment factor in tumors and expression of C regulatory proteins affect markedly the efficacy of immunochemotherapy. This data can be used to identify more accurately the patients for whom immunochemotherapy is given. It may also be beneficial in development of rituximab-containing and other monoclonal antibody therapies against cancer.