The mechanisms of Chansu in inducing efficient apoptosis in colon cancer cells

Chansu is one of the most widely used traditional Chinese medicines in China, Japan, and other Southeast Asian countries primarily for antipain, anti-inflammation, and recently anticancer. Over 10 recipes and remedies contained Chansu, which are easily available in pharmacies and hospitals, but the mechanisms of action were not clearly articulated. In the present study, Cinobufagin (CBF), the major compound of Chansu, was employed as a surrogate marker to determine its ability in inducing cancer cell death. As expected, CBF has significant cancer-killing capacity for a range of cancers, but such ability differs markedly. Colon and prostate cancers are more sensitive than skin and lung cancers. Interestingly, cancer cells die through apoptotic pathway either being biphasic caspase- 3-dependent (HCT116) or independent (HT29). Multipathway analysis reveals that CBF-induced apoptosis is likely modulated by the hypoxia-inducing factor-1 alpha subunit (HIF-1

Distinguishing between mathematics classrooms in Australia, China, Japan, Korea and the USA through the lens of the distribution of responsibility for knowledge generation : public oral interactivity and mathematical orality

The research reported in this paper examined spoken mathematics in particular well-taught classrooms in Australia, China (both Shanghai and Hong Kong), Japan, Korea and the USA from the perspective of the distribution of responsibility for knowledge generation in order to identify similarities and differences in classroom practice and the implicit pedagogical principles that underlie those practices. The methodology of the Learner’s Perspective Study (LPS) documented the voicing of mathematical ideas in public discussion and in teacher-student conversations and the relative priority accorded by different teachers to student oral contributions to classroom activity. Significant differences were identified among the classrooms studied, challenging simplistic characterisations of ‘the Asian classroom’ as enacting a single pedagogy, and suggesting that, irrespective of cultural similarities, local pedagogies reflect very different assumptions about learning and instruction. We have employed spoken mathematical terms as a form of surrogate variable, possibly indicative of the location of the agency for knowledge generation in the various classrooms studied (but also of interest in itself). The analysis distinguished one classroom from another on the basis of “public oral interactivity” (the number of utterances in whole class and teacher-student interactions in each lesson) and “mathematical orality” (the frequency of occurrence of key mathematical terms in each lesson). Classrooms characterized by high public oral interactivity were not necessarily sites of high mathematical orality. In particular, the results suggest that one characteristic that might be identified with a national norm of practice could be the level of mathematical orality: relatively high mathematical orality characterising the mathematics classes in Shanghai with some consistency, while lessons in Seoul and Hong Kong consistently involved much less frequent spoken mathematical terms. The relative contributions of teacher and students to this spoken mathematics provided an indication of how the responsibility for knowledge generation was shared between teacher and student in those classrooms. Specific analysis of the patterns of interaction by which key mathematical terms were introduced or solicited revealed significant differences. It is suggested that the empirical investigation of mathematical orality and its likely connection to the distribution of the responsibility for knowledge generation are central to the development of any theory of mathematics instruction.

Firefighter feedback during active cooling: A useful tool for heat stress management?

Monitoring an individual's thermic state in the workplace requires reliable feedback of their core temperature. However, core temperature measurement technology is expensive, invasive and often impractical in operational environments, warranting investigation of surrogate measures which could be used to predict core temperature. This study examines an alternative measure of an individual's thermic state, thermal sensation, which presents a more manageable and practical solution for Australian firefighters operating on the fireground. Across three environmental conditions (cold, warm, hot & humid), 49 Australian volunteer firefighters performed a 20-min fire suppression activity, immediately followed by 20min of active cooling using hand and forearm immersion techniques. Core temperature (Tc) and thermal sensation (TS) were measured across the rehabilitation period at five minute intervals. Despite the decline in Tc and TS throughout the rehabilitation period, there was little similarity in the magnitude or rate of decline between each measure in any of the ambient conditions. Moderate to strong correlations existed between Tc and TS in the cool (0.41, p<0.05) and hot & humid (0.57, p<0.05) conditions, however this was resultant in strong correlation during the earlier stages of rehabilitation (first five minutes), which were not evident in the latter stages. Linear regression revealed TS to be a poor predictor of Tc in all conditions (SEE=0.45-0.54°C) with a strong trend for TS to over-predict Tc (77-80% of the time). There is minimal evidence to suggest that ratings of thermal sensation, which represent a psychophysical assessment of an individual's thermal comfort, are an accurate reflection of the response of an individual's core temperature. Ratings of thermal sensation can be highly variable amongst individuals, likely moderated by local skin temperature. In account of these findings, fire managers require a more reliable source of information to guide decisions of heat stress management.

International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients.

A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation.

Effect of ECG-derived respiration (EDR) on modeling ventricular repolarization dynamics in different physiological and psychological conditions

Ventricular repolarization dynamics is an important predictor of the outcome in cardiovascular diseases. Mathematical modeling of the heart rate variability (RR interval variability) and ventricular repolarization variability (QT interval variability) is one of the popular methods to understand the dynamics of ventricular repolarization. Although ECG derived respiration (EDR) was previously suggested as a surrogate of respiration, but the effect of respiratory movement on ventricular repolarization dynamics was not studied. In this study, the importance of considering the effect of respiration and the validity of using EDR as a surrogate of respiration for linear parametric modeling of ventricular repolarization variability is studied in two cases with different physiological and psychological conditions. In the first case study, we used 20 young and 20 old healthy subjects’ ECG and respiration data from Fantasia database at Physionet to analyze a bivariate QT–RR and a trivariate QT–RR–RESP or QT–RR–EDR model structure to study the aging effect on cardiac repolarization variability. In the second study, we used 16 healthy subjects’ data from drivedb (stress detection for automobile drivers) database at Physionet to do the same analysis for different psychological condition (i.e., in stressed and no stress condition). The results of our study showed that model having respiratory information (QT–RR–RESP and QT–RR–EDR) gave significantly better fit value (p < 0.05) than that of found from the QT–RR model. EDR showed statistically similar (p > 0.05) performance as that of respiration as an exogenous model input in describing repolarization variability irrespective of age and different mental conditions. Another finding of our study is that both respiration and EDR-based models can significantly (p < 0.05) differentiate the ventricular repolarization dynamics between healthy subjects of different age groups and with different psychological conditions, whereas models without respiration or EDR cannot distinguish between the groups. These results established the importance of using respiration and the validity of using EDR as a surrogate of respiration in the absence of respiration signal recording in linear parametric modeling of ventricular repolarization variability in healthy subjects.

Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

FRAX (Aus) and falls risk: Association in men and women

Purpose: The WHO fracture risk prediction tool (FRAX®) utilises clinical risk factors to estimate the probability of fracture over a 10-year period. Although falls increase fracture risk, they have not been incorporated into FRAX. It is currently unclear if FRAX captures falls risk and whether addition of falls would improve fracture prediction. We aimed to investigate the association of falls risk and Australian-specific FRAX. Methods: Clinical risk factors were documented for 735 men and 602 women (age 40-90. yr) assessed at follow-up (2006-2010 and 2000-2003, respectively) of the Geelong Osteoporosis Study. FRAX scores with and without BMD were calculated. A falls risk score was determined at the time of BMD assessment and self-reported incident falls were documented from questionnaires returned one year later. Multivariable analyses were performed to determine: (i) cross-sectional association between FRAX scores and falls risk score (Elderly Falls Screening Test, EFST) and (ii) prospective relationship between FRAX and time to a fall. Results: There was an association between FRAX (hip with BMD) and EFST scores (. β=. 0.07, p<. 0.001). After adjustment for sex and age, the relationship became non-significant (. β=. 0.00, p=. 0.79). The risk of incident falls increased with increasing FRAX (hip with BMD) score (unadjusted HR 1.04, 95% CI 1.02, 1.07). After adjustment for age and sex, the relationship became non-significant (1.01, 95% CI 0.97, 1.05). Conclusions: There is a weak positive correlation between FRAX and falls risk score, that is likely explained by the inclusion of age and sex in the FRAX model. These data suggest that FRAX score may not be a robust surrogate for falls risk and that inclusion of falls in fracture risk assessment should be further explored.

Acute human lethal toxicity of agricultural pesticides: a prospective cohort study

BACKGROUND: agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000-370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. METHODS AND FINDINGS: we examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides-from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. CONCLUSION: the human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner.

The creation of international commercial law: Sovereignty felled?

The creation of international commercial law presents an interesting paradox for proponents of sovereignty in international law. Indeed, it could be argued that the creation of international commercial law is the vanishing point of sovereignty in that nation states are becoming increasingly less important in the creation of international commercial law with the growth of regional organizations, non-state actors, and international arbitration. This is spurred on by the march of globalization and the consequent need for international commercial law. The term "harmonization" will be used as a surrogate to discuss the creation of international commercial law, as it is the primary means by which international commercial law is created. This article seeks to chart this trend and show that nation states are being marginalized and will become significantly less relevant as more and more international legal instruments are created. In Part II, I paint the landscape against which the process is evolving; in Part III, I will demonstrate the growing role of regional endeavors at harmonization; and in Part IV, I will attempt to draw broad themes that establish that nation states will increasingly have a secondary role in the creation of international commercial law.

New trends in the making of international commercial law

This paper analyzes trends in the making of international commercial law including the impetus for generating conventions, the growth of regional conventions, and soft law.There has never been a better time to be an international commercial law scholar. After decades of being held hostage to state-centered ideas, international commercial law has finally broken through to become more solution oriented. Increasingly, nation states are becoming less important in the creation of international commercial law with the growth of regional organizations, non-state actors, and international arbitration. This is spurred on by the march of globalization and the need for international commercial law. The term "harmonization will be used as a surrogate to discuss the creation of international commercial law as it is the primary means by which international commercial law is created. This article seeks to explore two preponderant trends that have become visible in the making of international commercial law. In Part I, I shall describe the background. In Parts II and III, I will highlight the growing role of regional endeavors at harmonization, and the rise of non-binding instruments.

Testing the focal species approach to making conservation decisions for species persistence

Aim: Most risk assessments and decisions in conservation are based on surrogate approaches, where a group of species or environmental indicators are selected as proxies for other aspects of biodiversity. In the focal species approach, a suite of species is selected based on life history characteristics, such as dispersal limitation and area requirements. Testing the validity of the focal species concept has proved difficult, due to a lack of theory justifying the underlying framework, explicit objectives and measures of success. We sought to understand the conditions under which the focal species concept has merit for conservation decisions. Location: Our model system comprised 10 vertebrate species in 39 patches of native forest embedded in pine plantation in New South Wales, Australia. Methods: We selected three focal species based on ecological traits. We used a multiple-species reserve selection method that minimizes the expected loss of species, by estimating the risk of extinction with a metapopulation model. We found optimal reserve solutions for multiple species, including all 10 species, the three focal species, for all possible combinations of three species, and for each species individually. Results: Our case study suggests that the focal species approach can work: the reserve system that minimized the expected loss of the focal species also minimized the expected species loss in the larger set of 10 species. How well the solution would perform for other species and given landscape dynamics remains unknown. Main conclusions: The focal species approach may have merit as a conservation short cut if placed within a quantitative decision-making framework, where the aspects of biodiversity for which the focal species act as proxies are explicitly defined, and success is determined by whether the use of the proxy results in the same decision. Our methods provide a framework for testing other surrogate approaches used in conservation decision-making and risk assessment. © 2013 John Wiley & Sons Ltd.

Predictive mapping of abalone fishing grounds using remotely-sensed LiDAR and commercial catch data

Defining the geographic extent of suitable fishing grounds at a scale relevant to resource exploitation for commercial benthic species can be problematic. Bathymetric light detection and ranging (LiDAR) systems provide an opportunity to enhance ecosystem-based fisheries management strategies for coastally distributed benthic fisheries. In this study we define the spatial extent of suitable fishing grounds for the blacklip abalone (Haliotis rubra) along 200 linear kilometers of coastal waters for the first time, demonstrating the potential for integration of remotely-sensed data with commercial catch information. Variables representing seafloor structure, generated from airborne bathymetric LiDAR were combined with spatially-explicit fishing event data, to characterize the geographic footprint of the western Victorian abalone fishery, in south-east Australia. A MaxEnt modeling approach determined that bathymetry, rugosity and complexity were the three most important predictors in defining suitable fishing grounds (AUC = 0.89). Suitable fishing grounds predicted by the model showed a good relationship with catch statistics within each sub-zone of the fishery, suggesting that model outputs may be a useful surrogate for potential catch.

Trials and tribulations with electronic medication adherence monitoring in kidney transplantation

Medication adherence in kidney transplantation is critical to prevent graft rejection. Testing interventions designed to support patients to take their prescribed medications following a kidney transplant require an accurate measure of medication adherence. In research, the available methods for measuring medication adherence include self-report, pill counts, prescription refill records, surrogate measures of medication adherence and medication bottles with a microchip-embedded cap to record bottle openings. Medication bottles with a microchip-embedded cap are currently regarded as the gold standard measure. This commentary outlines the challenges in measuring medication adherence using electronic medication monitoring of kidney transplant patients recruited from five sites. The challenges included obtaining unanimous stakeholder support for using this method, agreement on an index medication to measure, adequate preparation of the patient and training of pharmacy staff, and how to analyze data when periods of time were not recorded using the electronic adherence measure. Provision of this information will enable hospital and community pharmacists to implement approaches that promote the effective use of this adherence measure for optimal patient outcomes.

Phase asymmetry of heart rate variability signal

Heart rate asymmetry (HRA) is considered as a physiological phenomenon in healthy subjects. In this article, we propose a novel HRA index, Slope Index (SI), to quantify phase asymmetry of heart rate variability (HRV) system. We assessed the performance of proposed index in comparison with conventional (Guzik's Index (GI) and Porta's Index (PI)) HRA indices. As illustrative examples, we used two case studies: (i) differentiate physiologic RR series from synthetic RR series; and (ii) discriminate arrhythmia subjects from Healthy using beat-to-beat heart rate time series. The results showed that SI is a superior parameter than GI and PI for both case studies with maximum ROC area of 0.84 and 0.82 respectively. In contrast, GI and PI had ROC areas {0.78, 0.61} and {0.50, 0.56} in two case studies respectively. We also performed surrogate analysis to show that phase asymmetry is caused by a physiologic phenomena rather than a random nature of the signal. In conclusion, quantification of phase asymmetry of HRV provides additional information on HRA, which might have a potential clinical use to discriminate pathological HRV in future.

Changes in intravenous fluid use patterns in Australia and New Zealand: evidence of research translating into practice

OBJECTIVES: To describe changes in the use of intravenous (IV) fluid by quantity and type in different regions of Australia and New Zealand. DESIGN, SETTING AND PARTICIPANTS: We conducted a retrospective ecological study examining regional and temporal trends in IV fluid consumption across Australia and New Zealand over the periods 2012-2013 and 2013- 2014, using national proprietary sales data as a surrogate for consumption, and demographic data from the public domain. RESULTS: More than 13.3 million litres of IV fluid were consumed in Australia and New Zealand in 2012-2013, and more than 13.9 million litres in 2013-2014, with colloid solutions accounting for < 2%. There was marked regional variation in consumption of fluids, by volumes and proportions used, when standardised to overall Australian and New Zealand values. There was no significant change in the overall volume of crystalloid solutions consumed but there was a significant decrease (9%; P = 0.02) in the ratio of unbalanced to balanced crystalloid solutions consumed. Consumption of all forms of colloid solutions decreased, with a 12% reduction overall (P = 0.02), primarily driven by a 67% reduction in the consumption of hydroxyethyl starch (HES) solutions. CONCLUSIONS: The amount and type of IV fluid use, as determined by fluid sales, is highly variable across Australia and New Zealand. However, overall use of balanced crystalloid solutions is increasing and the use of HES has decreased dramatically.