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.

Inhaled particle surface area dose: Stationary vs personal monitoring

The aim of this paper is to determine the suitability of solely stationary measurements for exposure assessment and management applications. For this purpose, quantified inhaled particle surface area (IPSA) doses using both stationary and personal particle exposure monitors were evaluated and compared.

Reducing pressure injuries in critically ill patients by using a patient skin integrity care bundle (InSPiRE)

Purpose To test an interventional patient skin integrity bundle, InSPiRE protocol, on the impact of pressure injuries (PrIs) in critically ill patients in an Australian adult intensive care unit (ICU). Methods Before and after design was used where the group of patients receiving the intervention (InSPiRE protocol) was compared with a similar control group who received standard care. Data collected included demographic and clinical variables, skin assessment, PrI presence and stage, and a Sequential Organ Failure Assessment (SOFA) score. Results Overall, 207 patients were enrolled, 105 in the intervention group and 102 in the control group. Most patients were men, mean age 55. The groups were similar on major demographic variables (age, SOFA scores, ICU length of stay). Pressure injury cumulative incidence was significantly lower in the intervention group (18%) compared to the control group for skin injuries(30.4%) (χ2=4.271, df=1, p=0.039) and mucous injuries (t test =3.27, p=<0.001) . Significantly fewer PrIs developing over time in the intervention group (Logrank= 11.842, df=1, p=<0.001) and patients developed fewer skin injuries (>3 PrIs/patient = 1/105) compared with the control group (>3 injuries/patient = 10/102) (p=0.018). Conclusion The intervention group, recieving the InSPiRE protocol, had lower PrI cumulative incidence, and reduced number and severity of PrIs that developed over time. Systematic and ongoing assessment of the patient's skin and PrI risk as well as implementation of tailored prevention measures are central to preventing PrIs.

Molecular recognition of 2,4,6-trinitrotoluene by 6-aminohexanethiol and surface-enhanced Raman scattering sensor

2,4,6-trinitrotoluene (TNT) is one of the most commonly used nitro aromatic explosives in landmine, military and mining industry. This article demonstrates rapid and selective identification of TNT by surface-enhanced Raman spectroscopy (SERS) using 6-aminohexanethiol (AHT) as a new recognition molecule. First, Meisenheimer complex formation between AHT and TNT is confirmed by the development of pink colour and appearance of new band around 500 nm in UV-visible spectrum. Solution Raman spectroscopy study also supported the AHT:TNT complex formation by demonstrating changes in the vibrational stretching of AHT molecule between 2800-3000 cm−1. For surface enhanced Raman spectroscopy analysis, a self-assembled monolayer (SAM) of AHT is formed over the gold nanostructure (AuNS) SERS substrate in order to selectively capture TNT onto the surface. Electrochemical desorption and X-ray photoelectron studies are performed over AHT SAM modified surface to examine the presence of free amine groups with appropriate orientation for complex formation. Further, AHT and butanethiol (BT) mixed monolayer system is explored to improve the AHT:TNT complex formation efficiency. Using a 9:1 AHT:BT mixed monolayer, a very low detection limit (LOD) of 100 fM TNT was realized. The new method delivers high selectivity towards TNT over 2,4 DNT and picric acid. Finally, real sample analysis is demonstrated by the extraction and SERS detection of 302 pM of TNT from spiked.

Practices to enhance peer program implementation integrity to safeguard peer leaders and learners

The powerful influence of peers on fellow students’ learning engagement and their ability to foster self-efficacy is well recognised. A positive learner mindset can be fostered through establishment of guided meaningful relationships formed between peers. Recognising the value of peer connections in shaping the student learning experience, peer programs have been widely adopted by universities as a mechanism to facilitate these connections. While potentially beneficial, a lack of knowledge and inexperience by program implementers can lead to program outcomes being compromised. To mitigate this risk, QUT has established university wide systems and benchmarks for enacting peer programs. These measures aim to promote program implementation integrity by supporting and developing the knowledge and capabilities of peer leaders and program coordinators. This paper describes a range of measures that have been instigated to optimise the quality of programs and ensure outcomes are mutually constructive and beneficial for all stakeholders.

Surface electromyography during physical exercise in water: A systematic review

Background Aquatic exercise has been widely used for rehabilitation and functional recovery due to its physical and physiological benefits. However, there is a high variability in reporting on the muscle activity from surface electromyographic (sEMG) signals. The aim of this study is to present an updated review of the literature on the state of the art of muscle activity recorded using sEMG during activities and exercise performed by humans in water. Methods A literature search was performed to identify studies of aquatic exercise movement. Results Twenty-one studies were selected for critical appraisal. Sample size, functional tasks analyzed, and muscles recorded were studied for each paper. The clinical contribution of the paper was evaluated. Conclusions Muscle activity tends to be lower in water-based compared to land-based activity; however more research is needed to understand why. Approaches from basic and applied sciences could support the understanding of relevant aspects for clinical practice.

Prediction of maximal surface electromyographically based voluntary contractions of erector spinae muscles from sonographic measurements during isometric contractions

Objectives Currently, there are no studies combining electromyography (EMG) and sonography to estimate the absolute and relative strength values of erector spinae (ES) muscles in healthy individuals. The purpose of this study was to establish whether the maximum voluntary contraction (MVC) of the ES during isometric contractions could be predicted from the changes in surface EMG as well as in fiber pennation and thickness as measured by sonography. Methods Thirty healthy adults performed 3 isometric extensions at 45° from the vertical to calculate the MVC force. Contractions at 33% and 100% of the MVC force were then used during sonographic and EMG recordings. These measurements were used to observe the architecture and function of the muscles during contraction. Statistical analysis was performed using bivariate regression and regression equations. Results The slope for each regression equation was statistically significant (P < .001) with R2 values of 0.837 and 0.986 for the right and left ES, respectively. The standard error estimate between the sonographic measurements and the regression-estimated pennation angles for the right and left ES were 0.10 and 0.02, respectively. Conclusions Erector spinae muscle activation can be predicted from the changes in fiber pennation during isometric contractions at 33% and 100% of the MVC force. These findings could be essential for developing a regression equation that could estimate the level of muscle activation from changes in the muscle architecture.

Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults

The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain.To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6. ±. 2.2. years; range: 20-29. years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity.FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=. 0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

Automated 3D mapping & shape analysis of the lateral ventricles via fluid registration of multiple surface-based atlases

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles, designed for monitoring degenerative disease effects in clinical neuroscience studies and drug trials. First we used a set of parameterized surfaces to represent the ventricles in a manually labeled set of 9 subjects' MRIs (atlases). We fluidly registered each of these atlases and mesh models to a set of MRIs from 12 Alzheimer's disease (AD) patients and 14 matched healthy elderly subjects, and we averaged the resulting meshes for each of these images. Validation experiments on expert segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease-related alterations monotonically improved as the number of atlases, N, was increased from 1 to 9. We then combined the segmentations with a radial mapping approach to localize ventricular shape differences in patients. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases, and we formulated a statistical stopping criterion to determine the optimal value of N. Anterior horn anomalies in Alzheimer's patients were only detected with the multi-atlas segmentation, which clearly outperformed the standard single-atlas approach.

Obesity gene NEGR1 associated with white matter integrity in healthy young adults

Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes - NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF- AS, ATXN2L, ATP2A1, KCTD15, and TNN13K - are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30. years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.

Genetic clustering on the hippocampal surface for genome-wide association studies

Imaging genetics aims to discover how variants in the human genome influence brain measures derived from images. Genome-wide association scans (GWAS) can screen the genome for common differences in our DNA that relate to brain measures. In small samples, GWAS has low power as individual gene effects are weak and one must also correct for multiple comparisons across the genome and the image. Here we extend recent work on genetic clustering of images, to analyze surface-based models of anatomy using GWAS. We performed spherical harmonic analysis of hippocampal surfaces, automatically extracted from brain MRI scans of 1254 subjects. We clustered hippocampal surface regions with common genetic influences by examining genetic correlations (r(g)) between the normalized deformation values at all pairs of surface points. Using genetic correlations to cluster surface measures, we were able to boost effect sizes for genetic associations, compared to clustering with traditional phenotypic correlations using Pearson's r.

Reducing structural variation to determine the genetics of white matter integrity across hemispheres - a dti study of 100 twins

Studies of cerebral asymmetry can open doors to understanding the functional specialization of each brain hemisphere, and how this is altered in disease. Here we examined hemispheric asymmetries in fiber architecture using diffusion tensor imaging (DTI) in 100 subjects, using high-dimensional fluid warping to disentangle shape differences from measures sensitive to myelination. Confounding effects of purely structural asymmetries were reduced by using co-registered structural images to fluidly warp 3D maps of fiber characteristics (fractional and geodesic anisotropy) to a structurally symmetric minimal deformation template (MDT). We performed a quantitative genetic analysis on 100 subjects to determine whether the sources of the remaining signal asymmetries were primarily genetic or environmental. A twin design was used to identify the heritable features of fiber asymmetry in various regions of interest, to further assist in the discovery of genes influencing brain micro-architecture and brain lateralization. Genetic influences and left/right asymmetries were detected in the fiber architecture of the frontal lobes, with minor differences depending on the choice of registration template.

Predicting white matter integrity from multiple common genetic variants

Several common genetic variants have recently been discovered that appear to influence white matter microstructure, as measured by diffusion tensor imaging (DTI). Each genetic variant explains only a small proportion of the variance in brain microstructure, so we set out to explore their combined effect on the white matter integrity of the corpus callosum. We measured six common candidate single-nucleotide polymorphisms (SNPs) in the COMT, NTRK1, BDNF, ErbB4, CLU, and HFE genes, and investigated their individual and aggregate effects on white matter structure in 395 healthy adult twins and siblings (age: 20-30 years). All subjects were scanned with 4-tesla 94-direction high angular resolution diffusion imaging. When combined using mixed-effects linear regression, a joint model based on five of the candidate SNPs (COMT, NTRK1, ErbB4, CLU, and HFE) explained ∼ 6% of the variance in the average fractional anisotropy (FA) of the corpus callosum. This predictive model had detectable effects on FA at 82% of the corpus callosum voxels, including the genu, body, and splenium. Predicting the brain's fiber microstructure from genotypes may ultimately help in early risk assessment, and eventually, in personalized treatment for neuropsychiatric disorders in which brain integrity and connectivity are affected.

Tensor-based analysis of genetic influences on brain integrity using DTI in 100 twins

Information from the full diffusion tensor (DT) was used to compute voxel-wise genetic contributions to brain fiber microstructure. First, we designed a new multivariate intraclass correlation formula in the log-Euclidean framework. We then analyzed used the full multivariate structure of the tensor in a multivariate version of a voxel-wise maximum-likelihood structural equation model (SEM) that computes the variance contributions in the DTs from genetic (A), common environmental (C) and unique environmental (E) factors. Our algorithm was tested on DT images from 25 identical and 25 fraternal twin pairs. After linear and fluid registration to a mean template, we computed the intraclass correlation and Falconer's heritability statistic for several scalar DT-derived measures and for the full multivariate tensors. Covariance matrices were found from the DTs, and inputted into SEM. Analyzing the full DT enhanced the detection of A and C effects. This approach should empower imaging genetics studies that use DTI.