Lactose surface modification by decantation: Are drug-fine lactose ratios the key to better dispersion of salmeterol xinafoate from lactose-interactive mixtures?

Purpose The role of fine lactose in the dispersion of salmeterol xinafoate (SX) from lactose mixtures was studied by modifying the fine lactose concentration on the surface of the lactose carriers using wet decantation. Methods Fine lactose was removed from lactose carriers by wet decantation using ethanol saturated with lactose. Particle sizing was achieved by laser diffraction. Fine particle fractions (FPFs) were determined by Twin Stage Impinger using a 2.5% SX mixture, and SX was analyzed by a validated high-performance liquid chromatography method. Adhesion forces between probes of SX and silica and the lactose surfaces were determined by atomic force microscopy. Results FPFs of SX were related to fine lactose concentration in the mixture for inhalation grade lactose samples. Reductions in FPF (2-4-fold) of Aeroflo 95 and 65 were observed after removing fine lactose by wet decantation; FPFs reverted to original values after addition of micronized lactose to decanted mixtures. FPFs of SX of sieved and decanted fractions of Aeroflo carriers were significantly different (p < 0.001). The relationship between FPF and fine lactose concentration was linear. Decanted lactose demonstrated surface modification through increased SX-lactose adhesion forces; however, any surface modification other than removal of fine lactose only slightly influenced FPF. Conclusions Fine lactose played a key and dominating role in controlling FPF. SX to fine lactose ratios influenced dispersion of SX with maximum dispersion occurring as the ratio approached unity.

Hepatitis C and initiates into injecting drug use among young people: Part I: The first shot

Explores how young people in Australia first come to inject drugs and how they learn about hepatitis C and sterile injecting drug use. Background on hepatitis C; Reasons for injecting drugs; Selection criteria for young people's participation in the i2i Project.

Molecular genetic investigation of mitochondrial dysfunction in relation to migraine susceptibility

The aim of this research was to assess the role of genetic variation in mitochondrial function and how this relates to migraine pathophysiology. Using our unique Norfolk Island population, a custom in-house next generation sequencing methodology was developed. This data for the first time showed that there is a molecular genetic link between mitochondrial dysfunction and migraine susceptibility. This work has provided the foundation for further studies aimed at utilising the identified markers in improved migraine diagnostic and therapeutic strategies.

Reliability of point-of-care testing of INR in acute stroke

Background In the emergency department, portable point-of-care testing (POCT) coagulation devices may facilitate stroke patient care by providing rapid International Normalized Ratio (INR) measurement. The objective of this study was to evaluate the reliability, validity, and impact on clinical decision-making of a POCT device for INR testing in the setting of acute ischemic stroke (AIS). Methods A total of 150 patients (50 healthy volunteers, 51 anticoagulated patients, 49 AIS patients) were assessed in a tertiary care facility. The INR's were measured using the Roche Coaguchek S and the standard laboratory technique. Results The interclass correlation coefficient and 95% confidence interval between overall POCT device and standard laboratory value INRs was high (0.932 (0.69 - 0.78). In the AIS group alone, the correlation coefficient and 95% CI was also high 0.937 (0.59 - 0.74) and diagnostic accuracy of the POCT device was 94%. Conclusions When used by a trained health professional in the emergency department to assess INR in acute ischemic stroke patients, the CoaguChek S is reliable and provides rapid results. However, as concordance with laboratory INR values decreases with higher INR values, it is recommended that with CoaguChek S INRs in the > 1.5 range, a standard laboratory measurement be used to confirm the results.

Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable disease occurring in one out of every 20,000 births. Although it is known that Type I collagen mutation in OI leads to increased bone fragility, the mechanism of this increased susceptibility to fracture is not clear. The aim of this study was to assess the microstructure of cortical bone fragments from patients with osteogenesis imperfecta (OI) using polarized light microscopy, and to correlate microstructural observations with the results of previously performed mechanical compression tests on bone from the same source. Specimens of cortical bone were harvested from the lower limbs of three (3) OI patients at the time of surgery, and were divided into two groups. Group 1 had been subjected to previous micro-mechanical compression testing, while Group 2 had not been subjected to any prior testing. Polarized light microscopy revealed disorganized bone collagen architecture as has been previously observed, as well as a large increase in the areal porosity of the bone compared to typical values for healthy cortical bone, with large (several hundred micron sized), asymmetrical pores. Importantly, the areal porosity of the OI bone samples in Group 1 appears to correlate strongly with their previously measured apparent Young's modulus and compressive strength. Taken together with prior nanoindentation studies on OI bone tissue, the results of this study suggest that increased intra-cortical porosity is responsible for the reduction in macroscopic mechanical properties of OI cortical bone, and therefore that in vivo imaging modalities with resolutions of ~ 100 μm or less could potentially be used to non-invasively assess bone strength in OI patients. Although the number of subjects in this study is small, these results highlight the importance of further studies in OI bone by groups with access to human OI tissue in order to clarify the relationship between increased porosity and reduced macroscopic mechanical integrity.

The high price of drug patents: Australia, patent law, pharmaceutical drugs and the Trans-Pacific Partnership

This week, the secrecy surrounding an independent Australian report on patent law and pharmaceutical drugs has been lifted, and the work has been published to great acclaim...

A comparison land-water environment of maximal voluntary isometric contraction during manual muscle testing through surface electromyography

Background The aim of this study was to compare through surface electromyographic (sEMG) recordings of the maximum voluntary contraction (MVC) on dry land and in water by manual muscle test (MMT). Method Sixteen healthy right-handed subjects (8 males and 8 females) participated in measurement of muscle activation of the right shoulder. The selected muscles were the cervical erector spinae, trapezius, pectoralis, anterior deltoid, middle deltoid, infraspinatus and latissimus dorsi. The MVC test conditions were random with respect to the order on the land/in water. Results For each muscle, the MVC test was performed and measured through sEMG to determine differences in muscle activation in both conditions. For all muscles except the latissimus dorsi, no significant differences were observed between land and water MVC scores (p = 0.063–0.679) and precision (%Diff = 7–10%) were observed between MVC conditions in the muscles trapezius, anterior deltoid and middle deltoid. Conclusions If the procedure for data collection is optimal, under MMT conditions it appears that comparable MVC sEMG values were achieved on land and in water and the integrity of the EMG recordings were maintained during wáter immersion.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

Mapping hippocampal and ventricular change in Alzheimer disease

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Fifty-two high-resolution MRI scans were acquired from 12 AD patients (age: 68.4 ± 1.9 years) and 14 matched controls (age: 71.4 ± 0.9 years), each scanned twice (2.1 ± 0.4 years apart). 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials.

The Step approach to Message Design and Testing (SatMDT): A conceptual framework to guide the development and evaluation of persuasive health messages

This paper provides an important and timely overview of a conceptual framework designed to assist with the development of message content, as well as the evaluation, of persuasive health messages. While an earlier version of this framework was presented in a prior publication by the authors in 2009, important refinements to the framework have seen it evolve in recent years, warranting the need for an updated review. This paper outlines the Step approach to Message Design and Testing (or SatMDT) in accordance with the theoretical evidence which underpins, as well as empirical evidence which demonstrates the relevance and feasibility, of each of the framework’s steps. The development and testing of the framework have thus far been based exclusively within the road safety advertising context; however, the view expressed herein is that the framework may have broader appeal and application to the health persuasion context.

The life of data: Evolving national testing

To this point, the collection has provided research-based, empirical accounts of the various and multiple effects of the National Assessment Program – Literacy and Numeracy (NAPLAN) in Australian schooling as a specific example of the global phenomenon of national testing. In this chapter, we want to develop a more theoretical analysis of national testing systems, globalising education policy and the promise of national testing as adaptive, online tests. These future moves claim to provide faster feedback and more useful diagnostic help for teachers. There is a utopian testing dream that one day adaptive, online tests will be responsive in real time providing an integrated personalised testing, pedagogy and intervention for each student. The moves towards these next generation assessments are well advanced, including the work of Pearson’s NextGen Learning and Assessment research group, the Organization for Economic Co-operation and Development’s (OECD) move into assessing affective skills and the Australian Curriculum, Assessment and Reporting Authority’s (ACARA) decision to phase in NAPLAN as an online, adaptive test from 2017...

National testing from an Australian perspective

Introduction This book examines a pressing educational issue: the global phenomenon of national testing in schooling and its vernacular development in Australia. The Australian National Assessment Program – Literacy and Numeracy (NAPLAN), introduced in 2008, involves annual census testing of students in Years 3, 5, 7 and 9 in nearly all Australian schools. In a variety of ways, NAPLAN affects the lives of Australia’s 3.5 million school students and their families, as well as more than 350,000 school staff and many other stakeholders in education. This book is organised in relation to a simple question: What are the effects of national testing for systems, schools and individuals? Of course, this simple question requires complex answers. The chapters in this edited collection consider issues relating to national testing policy, the construction of the test, usages of the testing data and various effects of testing in systems, schools and classrooms. Each chapter examines an aspect of national testing in Australia using evidence drawn from research. The final chapter by the editors of this collection provides a broader reflection on this phenomenon and situates developments in testing globally...

Local experiences, global similarities: Teacher perceptions of the impacts of national testing

Since 2008, Australian schoolchildren in Years 3, 5, 7 and 9 have sat a series of tests each May designed to assess their attainment of basic skills in literacy and numeracy. These tests are known as the National Assessment Program – Literacy and Numeracy (NAPLAN). In 2010, individual school NAPLAN data were first published on the MySchool website which enables comparisons to be made between individual schools and statistically like schools across Australia. NAPLAN represents the increased centrality of the federal government in education, particularly in regards to education policy. One effect of this has been a recast emphasis of education as an economic, rather than democratic, good. As Reid (2009) suggests, this recasting of education within national productivity agendas mobilises commonsense discourses of accountability and transparency. These are common articles of faith for many involved in education administration and bureaucracy; more and better data, and holding people to account for that data, must improve education...