A Randomized Combined Channel Approach for the Quantification of Color- and Intensity-Based Assays with Smartphones.

Quantification of colorimetric assays with smartphones is being increasingly reported. However, a complete characterization of the performance of existing color spaces and single-color channels for optimum color/intensity change quantification is absent. Moreover, it has not been ascertained if it is necessary to utilize existing color spaces to reach optimal assay quantification. In this study, a randomized channel approach was adapted utilizing all single channels from RGB, HSV, and CieLab color space and all nonrepeating random combinations of two and three channels of these color spaces. Assays based on color or intensity change using pH strips and gold or carbon black nanoparticle-containing paper strips were optimized using this approach. Several novel channel combinations showed great promise, in terms of prediction error and interphone variation reduction, outperforming RGB, HSV, and CieLab color spaces. These novel combinations were used in a custom-developed smartphone application that performed automated background subtraction and polynomial regression for the quantification of a lateral flow assay for the detection of goat milk adulteration with cow milk and for pH prediction in soil. For the lateral flow assay the channel combination BSA was found optimum (mean average error = 36% ± 6%; R2 = 0.97). For the soil pH assay the channel combination RLC was found optimum (mean average error = 1.31% ± 0.02%; R2 = 0.997). The study has shown that nonclassical channel combinations for colorimetric quantification of specific assays are very promising and should be considered for smartphone-based analysis.

The Efficiency of Color Space Channels to Quantify Color and Color Intensity Change in Liquids, pH Strips, and Lateral Flow Assays with Smartphones.

Bottom-up, end-user based feed, and food analysis through smartphone quantification of lateral flow assays (LFA) has the potential to cause a paradigm shift in testing capabilities. However, most developed devices do not test the presence of and implications of inter-phone variation. Much discussion remains regarding optimum color space for smartphone colorimetric analyses and, an in-depth comparison of color space performance is missing. Moreover, a light-shielding box is often used to avoid variations caused by background illumination while the use of such a bulky add-on may be avoidable through image background correction. Here, quantification performance of individual channels of RGB, HSV, and LAB color space and ΔRGB was determined for color and color intensity variation using pH strips, filter paper with dropped nanoparticles, and colored solutions. LAB and HSV color space channels never outperformed the best RGB channels in any test. Background correction avoided measurement variation if no direct sunlight was used and functioned more efficiently outside a light-shielding box (prediction errors < 5%/35% for color/color intensity change). The system was validated using various phones for quantification of major allergens (i.e., gluten in buffer, bovine milk in goat milk and goat cheese), and, pH in soil extracts with commercial pH strips and LFA. Inter-phone variation was significant for LFA quantification but low using pH strips (prediction errors < 10% for all six phones compared). Thus, assays based on color change hold the strongest promise for end-user adapted smartphone diagnostics.

The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.

Smartphone-based immunochemical sensor exploiting peroxidase-like activity of ligand-capped gold nanostars: A proof-of-concept detection of Mycobacterium bovis.

Bacterial pathogens represent a safety concern in the food industry, and this is amplified by the lack of sensing devices that can be applied on-site by non-trained personnel. In this study, peroxidase-mimicking activity of gold nanostars was exploited to develop a user-friendly colourimetric sensor. A smartphone was exploited as an image reader and analyser, empowered with a novel App developed in-house. The mobile App was evaluated and compared with a commercial smartphone App for its capability to quantify generated colourimetric signals. A major obstacle found with sensors relying on gold nanozymes is the fact that modification of the surface of gold nanoparticles with biorecognition elements generally lead to a suppression of their nanozyme activity. This drawback was overcome by introducing an autocatalytic growth step, which successfully restored the peroxidase-mimicking activity through generation of new gold nanoseeds acting as catalytic centres. A proof-of-concept using this sensing mechanism was developed targeting Mycobacterium bovis, a zoonotic pathogen primarily found in cattle but that can be transmitted to humans by consumption of contaminated food and cause tuberculosis disease. The resulting smartphone-based immunological sensor has shown promising results with a linear response between 104 - 106 CFU/mL, enabling detection of M. bovis at concentrations as low as 7.2·103 CFU/mL in buffer conditions. It is anticipated that the concept of the developed approach will have applicability in many fields relying on smartphone-based biosensing.

Color Alignment for Relative Color Constancy via Non-Standard References.

Relative colour constancy is an essential requirement for many scientific imaging applications. However, most digital cameras differ in their image formations and native sensor output is usually inaccessible, e.g., in smartphone camera applications. This makes it hard to achieve consistent colour assessment across a range of devices, and that undermines the performance of computer vision algorithms. To resolve this issue, we propose a colour alignment model that considers the camera image formation as a black-box and formulates colour alignment as a three-step process: camera response calibration, response linearisation, and colour matching. The proposed model works with non-standard colour references, i.e., colour patches without knowing the true colour values, by utilising a novel balance-of-linear-distances feature. It is equivalent to determining the camera parameters through an unsupervised process. It also works with a minimum number of corresponding colour patches across the images to be colour aligned to deliver the applicable processing. Three challenging image datasets collected by multiple cameras under various illumination and exposure conditions, including one that imitates uncommon scenes such as scientific imaging, were used to evaluate the model. Performance benchmarks demonstrated that our model achieved superior performance compared to other popular and state-of-the-art methods.

Global FKRP Registry: observations in more than 300 patients with Limb Girdle Muscular Dystrophy R9.

OBJECTIVE: The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin-Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP-related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities. METHODS: Registration is patient-initiated through a secure online portal. Data, reported by both patients and their clinicians, include: age of onset, presenting symptoms, family history, motor function and muscle strength, respiratory and cardiac function, medication, quality of life and pain. RESULTS: Of 663 registered participants, 305 were genetically confirmed LGMDR9 patients from 23 countries. A majority of LGMDR9 patients carried the common mutation c.826C > A on one or both alleles; 67.9% were homozygous and 28.5% were compound heterozygous for this mutation. The mean ages of symptom onset and disease diagnosis were higher in individuals homozygous for c.826C > A compared with individuals heterozygous for c.826C > A. This divergence was replicated in ages of loss of running ability, wheelchair-dependence and ventilation assistance; consistent with the milder phenotype associated with individuals homozygous for c.826C > A. In LGMDR9 patients, 75.1% were currently ambulant and 24.6%, nonambulant (unreported in 0.3%). Cardiac impairment was reported in 23.2% (30/129). INTERPRETATION: The Global FKRP Registry enables the collection of patient natural history data, which informs academics, healthcare professionals and industry. It represents a trial-ready cohort of individuals and is centrally placed to facilitate recruitment to clinical studies.

FPGA-Based Processor Acceleration for Image Processing Applications.

FPGA-based embedded image processing systems offer considerable computing resources but present programming challenges when compared to software systems. The paper describes an approach based on an FPGA-based soft processor called Image Processing Processor (IPPro) which can operate up to 337 MHz on a high-end Xilinx FPGA family and gives details of the dataflow-based programming environment. The approach is demonstrated for a k-means clustering operation and a traffic sign recognition application, both of which have been prototyped on an Avnet Zedboard that has Xilinx Zynq-7000 system-on-chip (SoC). A number of parallel dataflow mapping options were explored giving a speed-up of 8 times for the k-means clustering using 16 IPPro cores, and a speed-up of 9.6 times for the morphology filter operation of the traffic sign recognition using 16 IPPro cores compared to their equivalent ARM-based software implementations. We show that for k-means clustering, the 16 IPPro cores implementation is 57, 28 and 1.7 times more power efficient (fps/W) than ARM Cortex-A7 CPU, nVIDIA GeForce GTX980 GPU and ARM Mali-T628 embedded GPU respectively.

Nutrient effects on the calcium economy: emphasizing the potassium controversy.

The calcium economy is a dynamic state influenced by fluxes in dietary calcium intake, intestinal calcium absorption, and renal calcium conservation. The relationship of selected bone-related nutrients to these calcium fluxes exhibits both constructive and destructive interactions that affect the overall state of calcium balance. The basis of the calcium requirement and the impact of vitamin D, protein, phosphorus, sodium, and caffeine on the calcium economy are reviewed. Against this background, emerging data on potassium are presented. Data from balance studies of healthy white women at midlife were reviewed to assess the effect of diet potassium on the calcium economy under steady-state conditions. Potassium was inversely associated with both urinary calcium excretion and intestinal calcium absorption, yielding no significant net change in calcium balance. In the population reported on here, dairy, meat, and cereal grains together contributed 56%, and fruits and vegetables 44%, of total dietary potassium. To the extent that fruit and vegetable potassium is a surrogate for high bicarbonate, this cohort did not have a dietary intake pattern allowing for measurement or interpretation of the potential effect of a high-bicarbonate-containing diet on long-term steady-state calcium balance. Potassium itself is uniformly well absorbed regardless of the dietary source. Mean 24-h urinary potassium averaged 92% of dietary intake. According to nationwide food consumption surveys, milk is the number 1 single food source of potassium in all age groups in the United States.

FPGA-Based Soft-Core Processors for Image Processing Applications.

With security and surveillance, there is an increasing need to process image data efficiently and effectively either at source or in a large data network. Whilst a Field-Programmable Gate Array has been seen as a key technology for enabling this, the design process has been viewed as problematic in terms of the time and effort needed for implementation and verification. The work here proposes a different approach of using optimized FPGA-based soft-core processors which allows the user to exploit the task and data level parallelism to achieve the quality of dedicated FPGA implementations whilst reducing design time. The paper also reports some preliminary progress on the design flow to program the structure. An implementation for a Histogram of Gradients algorithm is also reported which shows that a performance of 328 fps can be achieved with this design approach, whilst avoiding the long design time, verification and debugging steps associated with conventional FPGA implementations.

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis.

This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging atom, [{(p-cym)Ru(II)X(N,N)}{H(+)}{(N,N)XRu(II)(p-cym)}][PF6] (N,N = functionalised quinaldamide and X = Cl or Br). These complexes are formed by a reaction of [p-cymRu(µ-X)2]2 with a functionalised quinaldamide ligand. When filtered over NH4PF6, and under aerobic conditions the equilibrium of NH4PF6 ⇔ NH3 + HPF6 enables incorporation of HPF6 and the stabilisation of two monomeric ruthenium complexes by a bridging H(+), which are counter-balanced by a PF6 counterion. X-ray crystallographic analysis is presented for six new structures with OO distances of 2.420(4)-2.448(15) Å, which is significant for strong hydrogen bonds. Chemosensitivity studies against HCT116, A2780 and cisplatin-resistant A2780cis human cancer cells showed the ruthenium complexes with a bromide ancillary ligand to be more potent than those with a chloride ligand. The 4'-fluoro compounds show a reduction in potency for both chloride and bromide complexes against all cell lines, but an increase in selectivity towards cancer cells compared to non-cancer ARPE-19 cells, with a selectivity index >1. Mechanistic studies showed a clear correlation between IC50 values and induction of cell death by apoptosis.

Design, set-up and utility of the UK facioscapulohumeral muscular dystrophy patient registry.

Facioscapulohumeral dystrophy (FSHD) is a rare inherited neuromuscular disease estimated to affect 1/15,000 people. Through basic research, remarkable progress has been made towards the development of targeted therapies. Patient identification, through registries or other means is essential for trial-readiness. The UK FSHD Patient Registry is a patient initiated registry that collects standardised and internationally agreed dataset of self-reported clinical details combined with professionally verified genetic information. It includes four additional questionnaires to capture patient reported outcomes related to pain, quality of life and scapular fixation. Between 2013 and 2015, 518 patients registered 243 males, 241 females with a mean age of 47.8 years. Most of the patients have FSHD type 1 (91.7 %), and weakness of the facial (59.2 %) was the most prevalent symptom at onset, followed by shoulder-girdle muscles (53.3 %) and distal (22.45 %) or proximal lower limb weakness (14.8 %). 85.57 % patients were ambulant or ambulant with assistance at the time of registration, 7.9 % report respiratory insufficiency. The registry has demonstrated utility with the recruitment of patients for a natural history study of infantile onset FSHD, and the longitudinal analysis of patient-related outcomes will provide much-needed baseline information to power future trials. The internationally agreed core dataset enables national registries to participate in a "Global FSHD registry". We suggest that the registry's ability to interoperate with other large datasets will be instrumental for sharing and exploiting data globally.

Calcium fortification systems differ in bioavailability.

The objective of this study was to compare the bioavailability of calcium from two fortification systems used in orange juice. The design was randomized crossover, within-subject. The subjects were 25 healthy premenopausal women in an academic health sciences center. Two commercially marketed calcium-fortified orange juices, ingested in an amount providing 500 mg calcium, were taken at breakfast after an overnight fast. The two fortification systems tested were calcium citrate malate and a combination of tricalcium phosphate and calcium lactate (tricalcium phosphate/calcium lactate). The main outcome measure was the area under the curve (AUC) for the increase in serum calcium from 0 to 9 hours after ingesting the test calcium source. Statistical analyses performed were repeated measures analysis of variance, testing source, and sequence. AUC 9 was 48% greater for calcium citrate malate than for tricalcium phosphate/calcium lactate ( P < .001); absorbed calcium calculated from AUC 9 values (mean+/-standard error of the mean) was 148+/-9.0 mg and 100+/-8.9 mg for calcium citrate malate and tricalcium phosphate/calcium lactate, respectively. The results indicate that equivalent calcium contents on a nutritional label do not guarantee equivalent nutritional value. Nutritionists and dietetics professionals should encourage manufacturers of fortified products to provide information on bioavailability.

Determinants of endogenous calcium entry into the gut.

BACKGROUND: In addition to food sources, calcium enters the gut by way of digestive secretions and shed mucosa. In health, such entry is as large as or larger than urinary calcium excretion. Because calcium absorption is inefficient, most of this endogenous intestinal calcium is excreted. OBJECTIVE: Our aim was to determine the dietary, anthropometric, and physiologic determinants of calcium entering the digestive stream from endogenous sources. DESIGN: Multiple regression modeling of intake and excretion data was used with 553 metabolic balance and kinetics studies performed in 190 midlife, white women. RESULTS: Endogenous intestinal calcium averaged 3.29 +/- 0.83 mmol/d. Multiple regression models explaining variation in this endogenous intestinal calcium were developed with use of dietary intake, anthropometric, and serum mineral variables. All 3 groups of predictor variables individually explained up to 22% of the variation in measured values for endogenous intestinal calcium. A composite model, incorporating all 3 groups explained 29% of the variation, with phosphorus and meat protein intakes, height, weight, and serum calcium and phosphorus concentrations all independently entering the model. Phosphorus intake dominated over all the other predictors, explaining 20% of the variance all by itself, with endogenous intestinal calcium rising by 0.037 mmol for every 1 mmol of phosphorus ingested. Meat protein (but not nonmeat protein) was the only other significant dietary contributor, exhibiting a negative coefficient. CONCLUSION: As a first approximation, the amount of endogenous calcium entering the digestive stream rises with body size and with the amount of phosphorus-rich food consumed.

The effect of soy protein isolate on bone metabolism.

OBJECTIVE: This double-blind, 15-month pilot study was designed to investigate the effect of soy protein isolate with varying concentrations of isoflavones on early postmenopausal bone loss and lipids. DESIGN: A total of 65 women, with a mean age of 55 years and 7.5 years since menopause, were randomized to one of three groups; soy protein with 96 mg isoflavones/day, soy with 52 mg isoflavones/day, or soy without isoflavones (< 4 mg isoflavones/day). Soy was given for 9 months and then discontinued; participants were followed for an additional 6 months. Bone mineral density (BMD) and blood lipids were measured during this time. RESULTS: Measurement of serum isoflavones at 3 months showed dose-related increases in the three groups. There was no significant effect of the soy supplements on BMD of the spine or femoral neck in any of the three groups. BMD increased significantly in the trochanter at 9 months (P = 0.0219) and at 15 months (P < 0.05) in the group given isoflavone-free soy compared with the other two groups. There was no significant effect of soy on lipid metabolism at the end of the intervention. CONCLUSION: The present study did not find a significant positive effect of soy protein isolate supplemented with isoflavones on BMD and the serum lipid profile in early postmenopausal women.

Decline in muscle mass with age in women: a longitudinal study using an indirect measure.

Muscle mass is known to decline with age, but only limited longitudinal data exist to quantify the rate of loss. Using 24-hour urine creatinine, corrected for the contribution of dietary meat intake, we assessed the change with age prospectively in 107 women who provided a minimum of 3 sets of measurements spanning an average interval of 11.9 years, centered around age 55 years. The rate of change in 24-hour urine creatinine at that age averaged -0.94%/yr (95% confidence interval [CI], -1.24% to -0.64%/yr; P <.001). Change in creatinine excretion was directly correlated with change in weight (P <.01), with those gaining weight tending to gain both lean and fat mass. The rate of change in creatinine excretion with age in our subjects is similar to that described in published cross-sectional studies on age-related change in total body potassium and in longitudinal studies using (40)K and dual-energy xray absorptiometry. Our study is the largest longitudinal study reported to date and provides, perhaps, a more secure basis for estimating muscle mass change with age than has been available heretofore.

Effect of yogurt on a urinary marker of bone resorption in postmenopausal women.

Adding three servings of yogurt to the daily diet of older women with habitually low calcium intakes resulted in a significant reduction in urinary excretion of N-telepeptide, a marker for bone resorption. Results were compared to the effects of three servings of a nutrition-poor snack and differences were apparent 7-10 days of starting the diet change. The satiety effect of the snacks resulted in a decrease in intake of other foods. The added nutrients of the yogurt improved overall diet quality substantially, while diet quality declined with the nutrient-poor snack. The results show that diets low in dairy intake are often marginal for several nutrients and that, so far as calcium is concerned, bone makes up for what the diet lacks. Moreover, bone resorption responds rapidly and sensitively to improvements in calcium intake that are readily achievable by an older female population.

Girls on a high-calcium diet gain weight at the same rate as girls on a normal diet: a pilot study.

OBJECTIVE: To determine whether pubertal girls assigned to calcium-rich diets or their usual calcium intakes differ significantly in weight gain. DESIGN: This is a pilot study conducted on data from an experimental research project. SUBJECTS/SETTING: The sample included 59 girls, 9 years of age, from Omaha metropolitan communities. INTERVENTION: Participants were randomly assigned to a calcium-rich diet supplying at least 1,500 mg of calcium per day or their usual diet. MAIN OUTCOME MEASURE: The outcome measure was change in weight during 2 years of study. STATISTICAL ANALYSES: Data were analyzed using descriptive statistics, Mann-Whitney U, t tests of paired and independent samples, and analysis of covariance. RESULTS: The girls in the calcium-rich diet group had a mean (+/-standard deviation) calcium intake of 1,656+/-191 mg/day, whereas the girls on their usual diets averaged 961+/-268 mg/day. Although the participants in the treatment group consumed nearly twice as much dietary calcium--primarily from dairy foods--they did not have greater increases in body weight, body mass index, or fat or lean mass than the control group. These findings held when the data were grouped by tertile of calcium intake. Compared with girls on their usual diets, the girls who consumed the calcium-rich diet also significantly increased their intake of essential nutrients. CONCLUSION: We conclude that calcium-rich diets do not cause excessive weight gain in pubertal girls but do contribute positively to overall nutrition. These findings provide support for programs to promote calcium-rich diets, which are critical for attaining peak bone mass.

The selection and prevalence of natural and fortified calcium food sources in the diets of adolescent girls.

OBJECTIVE: To assess the impact of calcium-fortified food and dairy food on selected nutrient intakes in the diets of adolescent girls. DESIGN: Randomized controlled trial, secondary analysis. SETTING AND PARTICIPANTS: Adolescent girls (n = 149) from a midwestern metropolitan area participated in randomized controlled trials of bone physiology from 1997 to 2008. INTERVENTION: Subjects randomly assigned to a high-calcium (HC) diet supplying 1,500 mg calcium/d, or their usual diet (UC). MAIN OUTCOME MEASURES: Dietary intake was assessed from 3-day food records and calcium intakes categorized by food source. Food group composites, representing calcium-fortified and dairy food categories, were examined for their relative nutrient contributions. Student t tests were used to evaluate differences in selected nutrient intakes between the 2 study groups. RESULTS: Dairy food contributed 68% of the total mean 1,494 mg calcium/d in the HC group, and calcium-fortified food contributed 304 mg calcium. In the UC group, dairy food contributed 69% of the total mean 765 mg calcium/d and calcium-fortified food contributed 50 mg calcium. Nutrient profiles of the dairy composites differed significantly from the calcium-fortified composites (P < .05). CONCLUSIONS AND IMPLICATIONS: Dairy food was the primary source of calcium selected by these adolescent girls; calcium-fortified food augmented calcium intakes.