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Variability in traits forming the Leaf Economics Spectrum (LES) among and within crop species play a key role in governing agroecosystem processes. However, studies evaluating the extent, causes, and consequences of within-species variation in LES traits for some of the world’s most common crops remain limited. We quantified variation in nine leaf traits measured across 90 vines of five wine grape (Vitis vinifera) varieties at two ontogenetic stages. Grape traits covary along an intraspecific LES, in patterns similar to those documented in wild plants. Across varieties, high rates of photosynthesis (A), and leaf nitrogen (N) concentrations, are coupled with low leaf mass per area (LMA), while the opposite suite of traits defines the “resource conserving end” of this intraspecific LES in grape. Variety identity predicted of leaf physiological (A) and morphological traits (i.e., leaf area and leaf mass), while leaf chemical traits and LMA were best explained by ontogenetic stage. All varieties expressed greater resource conserving trait syndromes (i.e., higher LMA, lower N, lower Amass) later in the growing season. Traits related to leaf hydraulics, including instantaneous water-use efficiency (WUE), were unrelated to LES and other resource capture traits, and were better explained by spatial location. Our results highlight the relative contributions of genetic vs. phenotypic factors in structuring this variation and point to a key role of domestication in governing trait relationships in the world’s crops.

Purpose To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. Design Retrospective image review. Participants Adults with diabetes mellitus. Methods All images from subjects with same-day UWF fluorescein angiography (FA) and color imaging were evaluated. Predominantly peripheral lesions (PPL) and DR severity were graded from UWF color images. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an optic disc centered inner and outer zone. Main Outcome Measures Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. Results Two hundred eighty-five eyes of 193 patients (24.9% mild nonproliferative DR [NPDR], 22.8% moderate NPDR, 37.5% severe NPDR and 14.7% proliferative DR [PDR]) were reviewed. No significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (quartile 1) were associated with a 1.7- to 2.4-fold nonperfusion increase across all retinal regions compared to the remaining eyes (P = 0.002 [PP] to 0.048 [FP]). In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (mild NPDR: 10% vs PDR: 31%, P = 0.007). This association was not observed when measured within the inner zone (P = 0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (quartile 1) was more common in eyes with PPL compared to eyes without PPL (34.1% vs 20.8%, P = 0.017) as were thicker outer venular calibers (quartile 4) (33% vs 21.3%, P = 0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7 ± 26.5μm vs 123.0 ± 29.5μm, P = 0.001). Conclusions The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.

Graham and Winkler derived a formula for the determinant of the distance matrix of a full-dimensional set of n + 1 points { x 0 , x 1 , … , x n } in the Hamming cube H n = ( { 0 , 1 } n , l 1 ) . In this article we derive a formula for the determinant of the distance matrix D of an arbitrary set of m + 1 points { x 0 , x 1 , … , x m } in H n . It follows from this more general formula that det ( D ) ≠ 0 if and only if the vectors x 0 , x 1 , … , x m are affinely independent. Specializing to the case m = n provides new insights into the original formula of Graham and Winkler. A significant difference that arises between the cases m n and m = n is noted. We also show that if D is the distance matrix of an unweighted tree on n + 1 vertices, then 〈 D − 1 1 , 1 〉 = 2 ∕ n where 1 is the column vector all of whose coordinates are 1. Finally, we derive a new proof of Murugan’s classification of the subsets of H n that have strict 1-negative type.

AIM: To evaluate the fractal feature of the retinal vasculature of normal eyes on a stereographic projected and montaged ultra-wide field (UWF) fluorescein angiography (FA). METHODS: Prospective, observational, cross-sectional study. Totally 59 eyes of 31 normal subjects were imaged using the Optos 200Tx. Images obtained at different gaze angles stereographically projected and montaged. The early-phase UWF FA frames were processed to segment the retinal vasculature and the results were exported as binary masks. The fractal dimension (FD) was calculated using the box-counting method. RESULTS: The global FD for the entire retina was 1.6±0.04, with no difference between males and females (1.59±0.04 vs 1.61±0.04, P=0.084) or between right and left eyes (1.6±0.04 vs 1.6±0.05, P=0.61). FD was non-uniformly distributed among four quadrants (P0.05). CONCLUSION: Fractal geometry is non-uniformly distributed across the retina in normal eyes and decreases from the fovea to the far-periphery. Subjects with an older age tend to have a smaller FD, however, the FD in the far-periphery does not appear to be influenced by age.

To quantify changes of the retinal vascular bed area (RVBA) in mm2 on stereographically projected ultrawide field fluorescein angiography images in eyes with proliferative diabetic retinopathy after antivascular endothelial growth factor injection.This is a prospective, observational study. The early-phase ultrawide field fluorescein angiography images (Optos 200Tx) of 40 eyes with proliferative diabetic retinopathy and significant nonperfusion obtained at baseline and after six months (NCT02863354) were stereographically projected by correcting peripheral distortion. The global retinal vasculature on ultrawide field fluorescein angiography was extracted for calculating RVBA by summing the real size (mm2) of all the pixels automatically.For the entire cohort, the global RVBA for the entire retina decreased from 67.1 ± 15.5 to 43.6 ± 18.8 mm2 after anti-VEGF treatment at six months (P0.001). In the subgroup receiving monthly anti-VEGF injections, the global RVBA decreased from 68.7 ± 16.2 to 33.9 ± 13.3 mm2 (P0.001). In the subgroup receiving anti-VEGF every three months, the global RVBA decreased from 65.6 ± 15.1 to 50.8 ± 19.3 mm2 (P = 0.004).RVBA seems to be a new biomarker to indicate efficiency of retinal vascular changes after anti-VEGF injection. Eyes with proliferative diabetic retinopathy and significant nonperfusion demonstrate reduced RVBA after anti-VEGF treatment.

To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA).Cross-sectional study.Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared.While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P.001). FD for the entire retina was negatively associated with global nonperfusion area (R = -0.44; P.001), and this relationship was also present within the 3 concentric retinal zones (posterior: R = -0.31, P = .016; midperiphery: R = -0.35, P = .007; and far periphery: R = -0.31, P = .015).Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.

We propose a convolutional neural network for localising the centres of the optic disc (OD) and fovea in ultra-wide field of view scanning laser ophthalmoscope (UWFoV-SLO) images of the retina. Images captured in both reflectance and autofluorescence (AF) modes, and central pole and eyesteered gazes, were used. The method achieved an OD localisation accuracy of 99.4% within one OD radius, and fovea localisation accuracy of 99.1% within one OD radius on a test set comprising of 1790 images. The performance of fovea localisation in AF images was comparable to the variation between human annotators at this task. The laterality of the image (whether the image is of the left or right eye) was inferred from the OD and fovea coordinates with an accuracy of 99.9%, Submitted to the 23rd Conference on Medical Image Understanding and Analysis (MIUA)

The classification of blood vessels into arterioles and venules is a fundamental step in the automatic investigation of retinal biomarkers for systemic diseases. In this paper, we present a novel technique for vessel classification on ultra-wide-field-of-view images of the retinal fundus acquired with a scanning laser ophthalmoscope. To the best of our knowledge, this is the first time that a fully automated artery/vein classification technique for this type of retinal imaging with no manual intervention has been presented. The proposed method exploits hand-crafted features based on local vessel intensity and vascular morphology to formulate a graph representation from which a globally optimal separation between the arterial and venular networks is computed by graph cut approach. The technique was tested on three different data sets (one publicly available and two local) and achieved an average classification accuracy of 0.883 in the largest data set.

The maximal roundness of a metric space is a quantity that arose in the study of embeddings and renormings. In the setting of Banach spaces, it was shown by Enflo that roundness takes on a much simpler form. In this paper we provide simple computations of the roundness of many standard Banach spaces, such as $\ell^{p}$, the Lebesgue-Bochner spaces $\ell^{p}(\ell^{q})$ and the Schatten ideals $S_{p}$. We also introduce a property that is dual to that of roundness, which we call coroundness, and make explicit the relation of these properties to the geometric concepts of smoothness and convexity of Banach spaces. Building off the work of Enflo, we are then able to provide multiple non-trivial equivalent conditions for a Banach space to possess maximal roundness greater than $1$. Using these conditions, we are able to conclude that certain Orlicz spaces possess non-trivial values of roundness and coroundness. Finally, we also use these conditions to provide an explicit example of a $2$-dimensional Banach space whose maximal roundness is not equal to that of its dual., 34 pages

A useful tool for computing the maximal generalised roundness of a finite metric space is a formula of Sánchez. Using well-known properties of the classical Cayley-Menger and Gramian matrices, we provide two simplifications of Sánchez’s formula that in particular do not require the calculation of any matrix inverses. To demonstrate the usefulness of these two new formulas we provide a simpler proof of Murugan’s classification of the subsets of the Hamming cube that have maximal generalised roundness greater than 1 1 .

AimsTo quantify retinal vascular bed area (RVBA) in square millimetres on stereographically projected ultra-wide field (UWF) fluorescein angiography (FA) in eyes with diabetic retinopathy (DR).MethodsA prospective, observational study. Baseline Optos 200Tx UWF FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center to adjust for peripheral distortion. The early-phase FA frame was used to extract the retinal vasculature as a mask for calculating RVBA. The pixels of the retinal vasculature were automatically computed in square millimetres using manufacturer-provided software.ResultsEighteen of 80 diabetic eyes were excluded because image quality and contrast were insufficient for automatic extraction of the retinal vasculature from the background fluorescence. The remaining 62 eyes were included in the final analysis. In comparison with age-matched and sex-matched normal controls, eyes with DR had a higher global RVBA for the entire retina (p2) than in those with non-proliferative DR (56.2±16.6 mm2) or in normal controls (37.2±9.9 mm2). This tendency was also present in the posterior retina and mid-periphery but absent in the far-periphery. RVBA did not correlate with retinal ischaemia (p>0.05).ConclusionsEyes with DR harboured a larger global RVBA for the entire retina than normal controls, and RVBA appeared to indicate DR severity. However, this biomarker was not observed to be a good indicator of retinal ischaemia.

Study Design Randomized clinical trial. Background Motor control exercises are believed to improve coordination of the trunk muscles. It is unclear whether increases in trunk muscle thickness can be facilitated by approaches such as the McKenzie method. Furthermore, it is unclear which approach may have superior clinical outcomes. Objectives The primary aim was to compare the effects of the McKenzie method and motor control exercises on trunk muscle recruitment in people with chronic low back pain classified with a directional preference. The secondary aim was to conduct a between-group comparison of outcomes for pain, function, and global perceived effect. Methods Seventy people with chronic low back pain who demonstrated a directional preference using the McKenzie assessment were randomized to receive 12 treatments over 8 weeks with the McKenzie method or with motor control approaches. All outcomes were collected at baseline and at 8-week follow-up by blinded assessors. Results No significant between-group difference was found for trunk muscle thickness of the transversus abdominis (-5.8%; 95% confidence interval [CI]: -15.2%, 3.7%), obliquus internus (-0.7%; 95% CI: -6.6%, 5.2%), and obliquus externus (1.2%; 95% CI: -4.3%, 6.8%). Perceived recovery was slightly superior in the McKenzie group (-0.8; 95% CI: -1.5, -0.1) on a -5 to +5 scale. No significant between-group differences were found for pain or function (P = .99 and P = .26, respectively). Conclusion We found no significant effect of treatment group for trunk muscle thickness. Participants reported a slightly greater sense of perceived recovery with the McKenzie method than with the motor control approach. Level of Evidence Therapy, level 1b-. Registered September 7, 2011 at www.anzctr.org.au (ACTRN12611000971932). J Orthop Sports Phys Ther 2016;46(7):514-522. Epub 12 May 2016. doi:10.2519/jospt.2016.6379.

Hyperproliferative cancer cells face increased replication stress, which can result in accumulation of DNA damage. As DNA damage can arrest proliferation, and, in the case of myeloid leukemia, induce differentiation of cancer cells, understanding the mechanisms that regulate the replication stress response is paramount. Here, we show that PARI, a replisome protein involved in regulating DNA repair and replication stress, suppresses differentiation of myeloid leukemia cells. We show that PARI is overexpressed in myeloid leukemia cells, and its knockdown reduces leukemia cell proliferation in vitro and in vivo in xenograft mouse models. PARI depletion enhances replication stress and DNA-damage accumulation, coupled with increased myeloid differentiation. Mechanistically, we show that PARI inhibits activation of the NF-κB pathway, which can initiate p21-mediated differentiation and proliferation arrest. Finally, we show that PARI expression negatively correlates with expression of differentiation markers in clinical myeloid leukemia samples, suggesting that targeting PARI may restore differentiation ability of leukemia cells and antagonize their proliferation.

Fundus images from the left eyes of 440 subjects aged 50-59 years enrolled in the Northern Ireland Cohort of Longitudinal Ageing were analyzed. Subjects were categorized as normotensive or hypertensive, according to thresholds on systolic/diastolic blood pressure measurement (140/90 mm Hg) averaged over two sitting measurements in a clinical setting. A fully automatic system to analyze each image used conventional and deep neural network machine learning techniques to locate retinal landmarks and detect, classify and measure retinal vessels. From this data, a measure of the arteriolar-venular ratio (AVR) in the peripheral retina was calculated. Semi-automatic analysis was also performed. Results are presented in Table 1. Subjects had mean age of 54.6 ± 2.9 years; 56.1% (247 of 440) females, with 34.3% (151 of 440) subjects categorized as hypertensive. Narrower arterioles and smaller AVR were observed in subjects with hypertension. This was also observed in fully-automated analysis, however 4% (17 of 440) subjects failed to be processed by the system. In fully-automated analysis the area under a receiver operator characteristic curve of AVR for hypertensive status was 0.69 (95% CI, 0.63 to 0.74). Table 1 - Results for semi-automated and automated analysis of retinal vessel parameters. *p Automated measurement of AVR in ultra-widefield fundus imaging was associated with hypertension. With further development, such as evaluation against diagnosis of hypertension obtained from ambulatory blood pressure monitoring clinics, this system could become a test for undiagnosed hypertension in people attending routine eye health check-ups.

Made available in DSpace on 2020-12-10T17:00:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 International MDT Research Foundation Disability Services at Student Support from the University of Sydney Objective The primary objective of this study was to compare the long-term (1-year follow-up) effects of the McKenzie method and motor control exercises on trunk muscle thickness in people with chronic low back pain (LBP) and a directional preference. Design Randomized controlled trial. Setting A secondary public health facility in Sydney, Australia. Participants Seventy adults with greater than 3-month history of LBP and a directional preference. Interventions Participants were randomized to receive 12 treatments of either the McKenzie method or motor control exercises over 8-weeks. Outcome measures Muscle thickness of the transversus abdominis, obliquus internus, and obliquus externus measured from ultrasound images. Secondary outcomes included function, perceived recovery, and pain. Outcomes were collected at baseline, post intervention at 8-weeks, and at 1-year follow-up by blinded assessors. The current paper focuses on the 1-year follow-up. Results Fifty-eight participants completed data collection for the primary outcome at 1-year. There were no significant between group differences for changes in trunk muscle thickness for any of the three investigated muscles: transversus abdominis [3%, 95% confidence interval (CI): 5%, 11%], obliquus internus [-4%, 95% CI: 9%, 2%] and obliquus externus [3%, 95% CI: 4%, 11%]. Similarly, there were no significant differences between groups for the secondary outcomes of function, perceived recovery and pain. Conclusion Trunk muscle thickness, function, perceive recovery and pain are similar between patients receiving McKenzie method or motor control exercises at a 1-year follow-up in a population of people with chronic LBP and a directional preference. (C) 2019 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved. Concord Repatriat Gen Hosp, Hosp Rd, Concord, Australia Univ Sydney, Fac Hlth Sci, Discipline Physiotherapy, 75 East St, Lidcombe, Australia Macquarie Univ, Fac Med & Hlth Sci, Herring Rd, N Ryde, NSW, Australia Helen Clare Physiotherapy, 263 Pacific Highway, Crows Nest, Australia Sao Paulo State Univ, Dept Phys Therapy, Fac Sci & Technol, Sao Paulo, SP, Brazil Sao Paulo State Univ, Dept Phys Therapy, Fac Sci & Technol, Sao Paulo, SP, Brazil

Retinal imaging with a fundus camera or scanning laser ophthalmoscope (SLO) allows a fast, non-invasive view to the body’s microvasculature. Evidence suggests that features associated with retinal blood vessels (for example, narrowing of arteries and increased vascular tortuosity) measured near to the optic disc are early biomarkers of disease such as diabetes, hypertension (HT) and cardiovascular disease. Ultra-widefield (UWF) ophthalmic imaging allows unique views of peripheral locations as well as the posterior pole, potentially facilitating a more comprehensive study of the state or health of the microvasculature than is afforded by conventional retinal imaging. It is envisaged that this will reveal new candidate biomarkers derivable from the retina which could help identify the presence of disease or improve risk stratification for serious illness. In this thesis, 532 individuals were recruited from a trial evaluating the added benefit of using computed tomography (CT) imaging in the diagnosis of coronary heart disease (CHD) to measure atherosclerotic plaque in the arteries of the heart muscle tissue. The trial participants were deeply phenotyped which allowed access to additional information including: presence and severity of CHD, hypertensive status, presence of diabetes, age, gender, and smoking status (all risk factors commonly associated with CHD). After CT imaging patients were invited for undilated UWF ophthalmic imaging using an Optos P200C SLO. To accurately measure features of blood vessels indicative of microvascular health or disease in these images required the development of a novel semi-automatic computerised technique to segment and analyse the retinal vasculature. This involved implementation of a supervised vessel segmentation algorithm utilising multi-scale matched filters, a neural network classifier and hysteresis thresholding. A true positive rate (TPR) of 0.702 (and standard deviation of 0.059), false positive rate (FPR) of 0.011 (0.006) and accuracy (Acc) of 0.965 (0.006) was achieved by the algorithm. This compared to TPR of 0.674 (0.062), FPR of 0.017 (0.004), and Acc of 0.957 (0.006) for state-of-the-art fundus camera vessel segmentation applied to UWF SLO. After segmentation and prior to the measurements of retinal vessel parameters, the distortions introduced by the instrument mapping the 3D retinal surface onto a 2D image plane were also accounted for utilising an established technique. This is especially important for measuring in the periphery of UWF images and has not previously been reported for biomarker discovery. Measurements from UWF SLO were compared between those participants with CHD (where a reduction in arterial width was hypothesised based on existing research with fundus cameras into cardiovascular disease), and those without to investigate whether a difference between the two groups existed. After appropriate statistical correction for confounding variables (i.e. age, gender, and hypertensive status) the results did not show a statistically significant difference for presence of CHD or for risk stratification. However, the analysis techniques that were developed in this thesis do allow a rapid investigation of retinal vascular parameters in UWF SLO. This has application to a number of other diseases, such as HT, where a more pronounced change to the appearance of vessels is anticipated, and to different areas of the peripheral retina not previously measurable with standard imaging techniques and existing algorithms.

PurposeReticular pseudodrusen (RPD) are a risk factor for late age-related macular degeneration (AMD). Associations between RPD and coronary artery disease (CAD) have been reported from small case–control studies. This study investigated the association of RPD within a predominantly CAD cohort.MethodsA subgroup of subjects from a multicentre randomised controlled trial of CT coronary angiography (CTCA) underwent ultrawide field (UWF) retinal imaging CAD determined by CTCA and was categorised as normal, non-obstructive or obstructive. Specific AMD features in UWF images were graded. Standardised grids were used to record the spatial location of AMD features, including RPD. Multivariate confounder adjusted regression models assessed the association between RPD and CAD.ResultsThe 534 participants were aged 27–75 years (mean 58±9 years; 425 (80%) ≥50 years) with a male preponderance (56%). Within the study sample, 178 (33%) had no CAD, 351 (66%) had CAD. RPD was detected in 30 participants (5.6%) and bilaterally in 23. Most participants with bilateral RPD had intermediate AMD 17 (74%). After adjustment for potential confounders (age, sex, drusen >125 µm, smoking status), multivariate analysis found no significant association between CAD and RPD (OR 1.31; 95% CI (0.57 to 3.01); p=0.52). A significant association was identified between RPD and intermediate AMD (OR 3.18; 95% CI (1.61 to 6.27); p=0.001).ConclusionWe found no evidence to support an association between CAD and RPD. RPD was strongly associated with intermediate AMD features.Trial registration numberNCT01149590, Post results.

ObjectiveChanges to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.MethodsWe retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal–annular arteriole:venule ratio (NA-AVR), a novel combined parameter.ResultsLeft and right eyes were analysed from 440 participants (aged 50–59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).ConclusionsSemiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.

Moseley AM, Herbert RD, Nightingale EJ, Taylor DA, Evans TM, Robertson GJ, Gupta SK, Penn J. Passive stretching does not enhance outcomes in patients with plantarflexion contracture after cast immobilization for ankle fracture: a randomized controlled trial. Arch Phys Med Rehabil 2005;86:1118–26. Objective To compare the efficacy of short- and long-duration passive stretches with a control treatment for the management of plantarflexion contracture after cast immobilization for ankle fracture. Design Assessor-blinded, randomized controlled trial. Setting Hospital physical therapy outpatient departments. Participants Adults with plantarflexion contracture (N=150) after cast immobilization for ankle fracture. All subjects were weight bearing or partial weight bearing. Interventions Exercise only, exercise plus short-duration passive stretch, and exercise plus long-duration passive stretch. All subjects had a 4-week course of exercises. In addition, subjects in the short-duration stretch plus exercise group completed 6 minutes of stretching per day, and subjects in the long-duration stretch plus exercise group completed 30 minutes of stretching per day. Main Outcome Measures Lower Extremity Functional Scale and passive dorsiflexion range of motion with the knee bent and straight at baseline, and at 4 weeks and 3 months postintervention. Results One hundred thirty-nine (93%) subjects completed the 4-week assessment and 134 (89%) subjects completed the 3-month assessment. There were no statistically significant or clinically important between-group differences for the primary outcomes. Conclusions The addition of passive stretching confers no benefit over exercise alone for the treatment of plantarflexion contracture after cast immobilization for ankle fracture.

Features of the retinal vasculature, such as vessel widths, are considered biomarkers for systemic disease. The aim of this work is to present a supervised approach to vessel segmentation in ultra-wide field of view scanning laser ophthalmoscope (UWFoV SLO) images and to evaluate its performance in terms of segmentation and vessel width estimation accuracy. The results of the proposed method are compared with ground truth measurements from human observers and with existing state-of-the-art techniques developed for fundus camera images that we optimized for UWFoV SLO images. Our algorithm is based on multi-scale matched filters, a neural network classifier and hysteresis thresholding. After spline-based refinement of the detected vessel contours, the vessel widths are estimated from the binary maps. Such analysis is performed on SLO images for the first time. The proposed method achieves the best results, both in vessel segmentation and in width estimation, in comparison to other automatic techniques.

Background: Informed consent is premised on the participants’ understanding the scope of the research and the associated risks and benefits. . The objective was to evaluate the improvement in knowledge in a population unfamiliar with clinical trial concepts about “what it means to be part of a clinical trial” using an innovative educational tool called the ‘Speaking Book’. Methods: This was a randomized controlled trial conducted at a research site in Uganda. 201 participants were randomized to: (1) clinical trials information session control arm, or (2) clinical trials information session followed by instruction in the use of the Speaking Book with a take-home copy (intervention arm). After the session, participants of both groups completed a 22-item multiple-choice test on the rights and responsibilities of participants. Participants returned after one week to complete the same test to assess knowledge retention. The mean pre- and post-test score difference was assessed according to trial arm using an unpaired t-test of proportions. Results: Ninety-one (90%) participants completed both the initial and follow-up tests in the control arm and 100 (100%) in the intervention arm. The average age of participants was 38 years, 53% were female and 67% were employed; 20% had previously been invited to participate in a clinical trial; of these, 19% had participated. The mean difference in proportion of correct responses from test 1 to test 2 was 2.7% (95%CI 0.3-5.0%) for the control arm and 11.6% (95%CI 9.3-13.7%) for the intervention arm (t-score=-5.3, p-value

Background: As the number of HIV infections continues to rise, the search for effective health education strategies must intensify. A new educational board game was developed to increase HIV peoples' attention and knowledge to HIV and sexually transmitted infections (STIs) information. The object of this study was to assess the effect of this educational board game on the uptake of knowledge. Methods: A randomized controlled trial where patients attending the Infectious Diseases Clinic, Kampala, Uganda were randomized to either play the board game (intervention arm) or to attend a health talk (standard of care arm). Participants' knowledge was assessed before and after the education sessions through a questionnaire. Results: One hundred eighty HIV-positive participants were enrolled, 90 for each study arm. The pretest scores were similar for each arm. There was a statistically significant increase in uptake of knowledge of HIV and STIs in both study arms. Compared with patients in the standard of care arm, participants randomized to the intervention arm had higher uptake of knowledge (4.7 points, 95% confidence interval: 3.9 to 5.4) than the controls (1.5 points, 95% confidence interval: 0.9 to 2.1) with a difference in knowledge uptake between arms of 3.2 points (P < 0.001). Additionally, both participants and facilitators preferred the board game to the health talk as education method. Conclusions: The educational game significantly resulted in higher uptake of knowledge of HIV and STIs. Further evaluation of the impact of this educational game on behavioral change in the short and long term is warranted.

BACKGROUND:: World Health Organization (WHO) immunological and clinical criteria for monitoring first-line antiretroviral treatment (ART) offer low accuracy for predicting viral failure. Targeting viral load assays to those at high risk has been recommended and a system to do this has been developed in Cambodia. Systems for use in Sub-Saharan African populations were evaluated. METHODS:: A new Ugandan based scoring system for targeting viral load assays was developed from data from the first 4 years of a Ugandan cohort (N = 559) receiving first-line ART. The accuracy of this, the Cambodian system and the WHO criteria to predict viral failure, through targeting viral load assays, were compared in a separate population of 496 Ugandans. RESULTS:: The new Ugandan scoring system included CD4 count, mean cell volume, adherence, and HIV associated clinical events as predictors of viral failure. In the validation population, the Ugandan system undertook viral load assays in 61 (12.3%) cases offering 20.5% sensitivity and 100% positive predictive value (PPV) to predict viral failure. The Cambodian system undertook viral load assays in 33 (6.7%) cases producing 23.1% sensitivity and 90.0% PPV. WHO criteria recommended viral load assays in 72 (14.5%) cases offering 30.8% sensitivity and 100% PPV. CONCLUSIONS:: Locally developed algorithms based on clinical and immunological criteria may offer little additional accuracy over WHO criteria for targeting viral load assays. Where possible, confirming viral load before switching therapy is recommended. Scoring systems are more flexible than WHO criteria in allowing ART providers to choose the proportion of the population that undergo targeted viral load testing.

Constitutively active mutant V600EB-RAF is present in 50% to 60% of sporadic melanomas and vemurafenib is a selective inactivating inhibitory drug. While the compound is initially effective in 80% patients, most of the patients eventually developed more invasive resistant disease. Unraveling the mechanisms leading to the development of vemurafenib resistance is key to developing better treatment strategies that can overcome the process and provide patients with more effective treatment options. Here we show that vemurafenib inhibits ERK activity to negatively regulate tumor suppressor Sprouty4 expression to increase Akt3 activity, leading to the development of drug-resistant melanomas. Combining vemurafenib with sigma receptor targeted LPD nanoparticle technology containing Akt3 siRNA and suppressor Sprouty4 plasmid simultaneously inhibit MAPK and Akt3, preventing resistant tumor development in xenografted mice. Our studies have identified a novel mechanism leading to the development of resistant melanoma following vemurafenib treatment and development of a novel melanoma cell targeting nanotechnology-based therapeutic agent for combating the development of resistance.

We explore post-processing of scanning laser ophthalmoscope (SLO) images for the automatic detection of retinal blood vessels. The retinal vasculature is first enhanced using morphological and Gaussian matched filters before a thresholding technique produces a binary vessel map. Such permutations of post-processing techniques are commonly used to achieve unsupervised classification of the vasculature in fundus images, and it is the purpose of this study to investigate their applicability to SLO imaging. We compare the results of vascular detection as performed on SLO and fundus images.