Exploring retinal markers of diabetic neuropathy

Purpose To investigate the application of retinal nerve fibre layer (RNFL) thickness as a marker for severity of diabetic peripheral neuropathy (DPN) in people with Type 2 diabetes. Methods This was a cross-sectional study whereby 61 participants (mean age 61 [41-75 years], mean duration of diabetes 14 [1-40 years], 70% male) with Type 2 diabetes and DPN underwent optical coherence tomography (OCT) scans. Global and 4 quadrant (TSNI) RNFL thicknesses were measured at 3.45mm around the optic nerve head of one eye. Neuropathy disability score (NDS) was used to assess the severity of DPN on a 0 to 10 scale. Participants were divided into three age-matched groups representing mild (NDS=3-5), moderate (NDS=6-8) and severe (NDS=9-10) neuropathy. Two regression models were fitted for statistical analysis: 1) NDS scores as co-variate for global and quadrant RNFL thicknesses, 2) NDS groups as a factor for global RNFL thickness only. Results Mean (SD) RNFL thickness (µm) was 103(9) for mild neuropathy (n=34), 101(10) for moderate neuropathy (n=16) and 95(13) in the group with severe neuropathy (n=11). Global RNFL thickness and NDS scores were statistically significantly related (b=-1.20, p=0.048). When neuropathy was assessed across groups, a trend of thinner mean RNFL thickness was observed with increasing severity of neuropathy; however, this result was not statistically significant (F=2.86, p=0.065). TSNI quadrant analysis showed that mean RNFL thickness reduction in the inferior quadrant was 2.55 µm per 1 unit increase in NDS score (p=0.005). However, the regression coefficients were not statistically significant for RNFL thickness in the superior (b=-1.0, p=0.271), temporal (b=-0.90, p=0.238) and nasal (b=-0.99, p=0.205) quadrants. Conclusions RNFL thickness was reduced with increasing severity of DPN and the effect was most evident in the inferior quadrant. Measuring RNFL thickness using OCT may prove to be a useful, non-invasive technique for identifying severity of DPN and may also provide additional insight into common mechanisms for peripheral neuropathy and RNFL damage.

Retinal nerve fibre layer thickness is associated with higher risk of foot ulceration in diabetic peripheral neuropathy

Purpose To evaluate the association between retinal nerve fibre layer (RNFL) thickness and diabetic peripheral neuropathy in people with type 2 diabetes, and specifically those at higher risk of foot ulceration. Methods RNFL thicknesses was measured globally and in four quadrants (temporal, superior, nasal and inferior) at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). Severity of neuropathy was assessed using the Neuropathy Disability Score (NDS). Eighty-two participants with type 2 diabetes were stratified according to NDS scores (0-10) as: none, mild, moderate, and severe neuropathy. A control group was additionally included (n=17). Individuals with NDS≥ 6 (moderate and severe neuropathy) have been shown to be at higher risk of foot ulceration. A linear regression model was used to determine the association between RNFL and severity of neuropathy. Age, disease duration and diabetic retinopathy levels were fitted in the models. Independent t-test was employed for comparison between controls and the group without neuropathy, as well as for comparison between groups with higher and lower risk of foot ulceration. Analysis of variance was used to compare across all NDS groups. Results RNFL thickness was significantly associated with NDS in the inferior quadrant (b= -1.46, p=0.03). RNFL thicknesses globally and in superior, temporal and nasal quadrants did not show significant associations with NDS (all p>0.51). These findings were independent of the effect of age, disease duration and retinopathy. RNFL was thinner for the group with NDS ≥ 6 in all quadrants but was significant only inferiorly (p<0.005). RNFL for control participants was not significantly different from the group with diabetes and no neuropathy (superior p=0.07, global and all other quadrants: p>0.23). Mean RNFL thickness was not significantly different between the four NDS groups globally and in all quadrants (p=0.08 for inferior, P>0.14 for all other comparisons). Conclusions Retinal nerve fibre layer thinning is associated with neuropathy in people with type 2 diabetes. This relationship is strongest in the inferior retina and in individuals at higher risk of foot ulceration.

Predicting the likelihood of QA failure using treatment plan accuracy metrics

This study used automated data processing techniques to calculate a set of novel treatment plan accuracy metrics, and investigate their usefulness as predictors of quality assurance (QA) success and failure. 151 beams from 23 prostate and cranial IMRT treatment plans were used in this study. These plans had been evaluated before treatment using measurements with a diode array system. The TADA software suite was adapted to allow automatic batch calculation of several proposed plan accuracy metrics, including mean field area, small-aperture, off-axis and closed-leaf factors. All of these results were compared the gamma pass rates from the QA measurements and correlations were investigated. The mean field area factor provided a threshold field size (5 cm2, equivalent to a 2.2 x 2.2 cm2 square field), below which all beams failed the QA tests. The small aperture score provided a useful predictor of plan failure, when averaged over all beams, despite being weakly correlated with gamma pass rates for individual beams. By contrast, the closed leaf and off-axis factors provided information about the geometric arrangement of the beam segments but were not useful for distinguishing between plans that passed and failed QA. This study has provided some simple tests for plan accuracy, which may help minimise time spent on QA assessments of treatments that are unlikely to pass.

A spatial-indexing model for measuring neighbourhood-level land-use and transport integration

Significant attention has been given in urban policy literature to the integration of land-use and transport planning and policies—with a view to curbing sprawling urban form and diminishing externalities associated with car-dependent travel patterns. By taking land-use and transport interaction into account, this debate mainly focuses on how a successful integration can contribute to societal well-being, providing efficient and balanced economic growth while accomplishing the goal of developing sustainable urban environments and communities. The integration is also a focal theme of contemporary urban development models, such as smart growth, liveable neighbourhoods, and new urbanism. Even though available planning policy options for ameliorating urban form and transport-related externalities have matured—owing to growing research and practice worldwide—there remains a lack of suitable evaluation models to reflect on the current status of urban form and travel problems or on the success of implemented integration policies. In this study we explore the applicability of indicator-based spatial indexing to assess land-use and transport integration at the neighbourhood level. For this, a spatial index is developed by a number of indicators compiled from international studies and trialled in Gold Coast, Queensland, Australia. The results of this modelling study reveal that it is possible to propose an effective metric to determine the success level of city plans considering their sustainability performance via composite indicator methodology. The model proved useful in demarcating areas where planning intervention is applicable, and in identifying the most suitable locations for future urban development and plan amendments. Lastly, we integrate variance-based sensitivity analysis with the spatial indexing method, and discuss the applicability of the model in other urban contexts.

An efficient synthesis of (±)-frondosin B using a Stille–Heck reaction sequence

A concise, convergent synthesis of (±)-frondosin B has been developed based on the application of a Stille–Heck reaction sequence of 2-chloro-5-methoxybenzo[b]furan-3-yl triflate and 2-(3-butenyl)-3-(trimethylstannyl)cyclohex-2-enone giving the racemic natural product in a 34% overall yield.

The molecular structure of the borate mineral rhodizite (K, Cs)Al4Be4(B, Be)12O28 – A vibrational spectroscopic study

We have studied the borate mineral rhodizite (K, Cs)Al4Be4(B, Be)12O28 using a combination of DEM with EDX and vibrational spectroscopic techniques. The mineral occurs as colorless, gray, yellow to white crystals in the triclinic crystal system. The studied sample is from the Antandrokomby Mine, Sahatany valley, Madagascar. The mineral is prized as a semi-precious jewel. Semi-quantitative chemical composition shows a Al, Ca, borate with minor amounts of K, Mg and Cs. The mineral has a characteristic borate Raman spectrum and bands are assigned to the stretching and bending modes of B, Be and Al. No Raman bands in the OH stretching region were observed.

Generation and characterization of ionic and neutral dihydroxy boron B(OH)(2)(+/0) in the gas phase

The dicoordinated borinium ion, dihydroxyborinium, B(OH)(2)(+) is generated from methyl boronic acid CH3B(OH)(2) by dissociative electron ionization and its connectivity confirmed by collisional activation. Neutralization-reionization (NR) experiments on this ion indicate that the neutral B(OH)(2) radical is a viable species in the gas phase. Both vertical neutralization of B(OH)(2)(+) and reionization of B(OH)(2) in the NR experiment are, however, associated with particularly unfavorable Franck-Condon factors. The differences in adiabatic and vertical electron transfer behavior can be traced back to a particular pi stabilization of the cationic species compared to the sp(2)-type neutral radical. Thermochemical data on several neutral and cationic boron compounds are presented based on calculations performed at the G2 level of theory.

Analysis of the NF-κB p50 dimer interface by diversity screening

An in vivo screen has been devised for NF-κB p50 activity in Escherichia coli exploiting the ability of the mammalian transcription factor to emulate a prokaryotic repressor. Active intracellular p50 was shown to repress the expression of a green fluorescent protein reporter gene allowing for visual screening of colonies expressing active p50 on agar plates. A library of mutants was constructed in which the residues Y267, L269, A308 and V310 of the dimer interface were simultaneously randomised and twenty-five novel functional interfaces were selected which repressed the reporter gene to similar levels as the wild-type protein. The leucine-269 alanine-308 core was repeatedly, but not exclusively, selected from the library whilst a diversity of predominantly non-polar residues were selected at positions 267 and 310. These results indicate that L269 and A308 may form a hot spot of interaction and allow an insight into the processes of dimer selectivity and evolution within this family of transcription factors.

Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes

The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.

Treatment plan complexity metrics for predicting IMRT pre-treatment quality assurance results

The planning of IMRT treatments requires a compromise between dose conformity (complexity) and deliverability. This study investigates established and novel treatment complexity metrics for 122 IMRT beams from prostate treatment plans. The Treatment and Dose Assessor software was used to extract the necessary data from exported treatment plan files and calculate the metrics. For most of the metrics, there was strong overlap between the calculated values for plans that passed and failed their quality assurance (QA) tests. However, statistically significant variation between plans that passed and failed QA measurements was found for the established modulation index and for a novel metric describing the proportion of small apertures in each beam. The ‘small aperture score’ provided threshold values which successfully distinguished deliverable treatment plans from plans that did not pass QA, with a low false negative rate.

Effects of small field output factors on IMRT optimisation and dose calculation

Introduction Given the known challenges of obtaining accurate measurements of small radiation fields, and the increasing use of small field segments in IMRT beams, this study examined the possible effects of referencing inaccurate field output factors in the planning of IMRT treatments. Methods This study used the Brainlab iPlan treatment planning system to devise IMRT treatment plans for delivery using the Brainlab m3 microMLC (Brainlab, Feldkirchen, Germany). Four pairs of sample IMRT treatments were planned using volumes, beams and prescriptions that were based on a set of test plans described in AAPM TG 119’s recommendations for the commissioning of IMRT treatment planning systems [1]: • C1, a set of three 4 cm volumes with different prescription doses, was modified to reduce the size of the PTV to 2 cm across and to include an OAR dose constraint for one of the other volumes. • C2, a prostate treatment, was planned as described by the TG 119 report [1]. • C3, a head-and-neck treatment with a PTV larger than 10 cm across, was excluded from the study. • C4, an 8 cm long C-shaped PTV surrounding a cylindrical OAR, was planned as described in the TG 119 report [1] and then replanned with the length of the PTV reduced to 4 cm. Both plans in each pair used the same beam angles, collimator angles, dose reference points, prescriptions and constraints. However, one of each pair of plans had its beam modulation optimisation and dose calculation completed with reference to existing iPlan beam data and the other had its beam modulation optimisation and dose calculation completed with reference to revised beam data. The beam data revisions consisted of increasing the field output factor for a 0.6 9 0.6 cm2 field by 17 % and increasing the field output factor for a 1.2 9 1.2 cm2 field by 3 %. Results The use of different beam data resulted in different optimisation results with different microMLC apertures and segment weightings between the two plans for each treatment, which led to large differences (up to 30 % with an average of 5 %) between reference point doses in each pair of plans. These point dose differences are more indicative of the modulation of the plans than of any clinically relevant changes to the overall PTV or OAR doses. By contrast, the maximum, minimum and mean doses to the PTVs and OARs were smaller (less than 1 %, for all beams in three out of four pairs of treatment plans) but are more clinically important. Of the four test cases, only the shortened (4 cm) version of TG 119’s C4 plan showed substantial differences between the overall doses calculated in the volumes of interest using the different sets of beam data and thereby suggested that treatment doses could be affected by changes to small field output factors. An analysis of the complexity of this pair of plans, using Crowe et al.’s TADA code [2], indicated that iPlan’s optimiser had produced IMRT segments comprised of larger numbers of small microMLC leaf separations than in the other three test cases. Conclusion: The use of altered small field output factors can result in substantially altered doses when large numbers of small leaf apertures are used to modulate the beams, even when treating relatively large volumes.

A nutrition and physical activity intervention for family child care homes

Background Family child care homes (FCCHs) provide child care to 1.9 million children in the U.S., but many do not meet established child care standards for healthy eating and physical activity. Purpose To determine the effects of a community-based train-the-trainer intervention on FCCHs policies and practices related to healthy eating and physical activity. Design Quasi-experimental design with replication in three independent cohorts of FCCHs. Setting/participants Registered FCCHs from 15 counties across Kansas participated in the Healthy Kansas Kids (HKK) program. Resource and referral agencies (RRAs) in each county recruited and enrolled between five and 15 child care providers in their service delivery area to participate in the program. The number of registered FCCHs participating in HKK in Years 1 (2006-2007); 2 (2007-2008); and 3 (2008-2009) of the program were 85, 64, and 87, respectively. A stratified random sample of registered FCCHs operating in Kansas (n=297) served as a normative comparison group. Interventions Child care trainers from each RRA completed a series of train-the-trainer workshops related to promotion of healthy eating and physical activity. FCCHs were subsequently guided through a four-step iterative process consisting of (1) self-evaluation; (2) goal setting; (3) developing an action plan; and (4) evaluating progress toward meeting goals. FCCHs also received U. S. Department of Agriculture resources related to healthy eating and physical activity. Main outcome measures Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) self-assessment instrument (NAP SACC-SA). Analyses of outcome measures were conducted between 2008 and 2010. Results Healthy Kansas Kids FCCHs exhibited significant improvements in healthy eating (Delta=6.9%-7.1%) and physical activity (Delta=15.4%-19.2%) scores (p<0.05). Within each cohort, pre-intervention scores were not significantly different from the state average, whereas post-intervention scores were significantly higher than the state average. Conclusions Community-based train-the-trainer interventions to promote healthy eating and physical activity in FCCHs are feasible, sustainable, and effective.

Securing medical devices Part B : what’s available for nasogastric tubes?

This article is the second part of a two-part series examining securement options for commonly used therapeutic devices in the adult intensive care unit. Part A focused on endotracheal device securement.1 This article addresses nasogastric tube (NGT) securement options and with the aim of identifying the available range of NGT securement devices in Australia as a resource for clinicians seeking to explore options for tube stabilisation. Nasogastric feeding or gastric decompression tubes are commonly inserted via the nostril/nares. The National Pressure Ulcer Advisory Panel (NPUAP) 2011 position statement on mucosal pressure injuries, highlighted that mucosal tissues are vulnerable to pressure from devices.2 Securing of these devices sometimes leads to pressure-related injury to the internal mucosa due to difficulty visualising the mucosa and failure to reposition the nasogastric tube to relieve the pressure in a particular area.3 The nasal orifice is much smaller than the oral cavity and regular tube position changes are vital to minimise the risk of mucosal damage and ulcer development.