Glycosylated gold nanoparticle libraries for label-free multiplexed lectin biosensing

Glycan/lectin interactions drive a wide range of recognition and signal transduction processes within nature. However, their measurement is complicated or limited by the analytical tools available. Most technologies require fluorescently labelled proteins (e.g. microarrays) or expensive infrastructure (such as surface plasmon resonance). This also limits their application in biosensing, especially for low-resource settings, where detection of pathogens based on glycan binding could speed up diagnosis. Here we employ a library-oriented approach to immobilise a range of monosaccharides onto polymer-stabilised gold nanoparticles to enable rapid and high-throughput evaluation of their binding specificities with a panel of lectins. The red to blue colour shift upon gold nanoparticle aggregation is used as the output, removing the need for labelled protein, enabling compatibility with 96-well microplates. Furthermore, we demonstrate the use of a flatbed scanner (or digital camera) to extract biophysical data, ensuring that only minimal resources are required. Finally, linear discriminant analysis is employed to demonstrate how the glyconanoparticles can be applied as a multiplexed biosensor capable of identifying pathogenic lectins without the need for any infrastructure and overcoming some of the issues of lectin promiscuity

Glycan heterogeneity on gold nanoparticles increases lectin discrimination capacity in label-free multiplexed bioassays

The development of new analytical tools as point-of-care biosensors is crucial to combat the spread of infectious diseases, especially in the context of drug-resistant organisms, or to detect biological warfare agents. Glycan/lectin interactions drive a wide range of recognition and signal transduction processes within nature and are often the first site of adhesion/recognition during infection making them appealing targets for biosensors. Glycosylated gold nanoparticles have been developed that change colour from red to blue upon interaction with carbohydrate-binding proteins and may find use as biosensors, but are limited by the inherent promiscuity of some of these interactions. Here we mimic the natural heterogeneity of cell-surface glycans by displaying mixed monolayers of glycans on the surface of gold nanoparticles. These are then used in a multiplexed, label-free bioassay to create ‘barcodes’ which describe the lectin based on its binding profile. The increased information content encoded by using complex mixtures of a few sugars, rather than increased numbers of different sugars makes this approach both scalable and accessible. These nanoparticles show increased lectin identification power at a range of lectin concentrations, relative to single-channel sensors. It was also found that some information about the concentration of the lectins can be extracted, all from just a simple colour change, taking this technology closer to being a realistic biosensor

Evaluation of pedotransfer functions to estimate some of soil hydraulic characteristics in North Africa: a case study from Morocco

Soil hydraulic properties are an important factor to optimize and adapt water management for a given crop. Pedotransfer functions (PTFs) present a solution to predict soil variables such as hydraulic properties, using fundamental soil properties. In this research, we compared two sources of soil information: iSDAsoil data and field data, in four regions in Morocco. We then used this data to evaluate published data and developed new PTFs using soil information to estimate soil gravimetric moisture content at saturation (w0), field capacity (w330) and permanent wilting point (w15000). A total of 331 samples were collected from four regions: Doukkala, Gharb-Loukous, Moulouya and Tadla. The data was divided into calibration and validation datasets. For development of different PTFs, we used simple linear regression, multiple linear regression, regression tree, Cubist algorithm, and random forest approaches. PTFs developed by Dijkerman (Geoderma, 1988, 42, 29–49) presented the best performance, showing lower RMSE, Bias and MAE compared to other PTFs. Using multiple linear regression to develop PTFs, models based on clay, silt and soil organic matter as input variables showed the best performance after calibration (R2 of 0.590, 0.785, 0.786 for w0, w330, and w15000, respectively). Regarding the techniques based on machine learning, random forest showed the best performance after calibration compared with other algorithms (R2 of 0.930, 0.955, 0.954 for w0, w330, and w15000, respectively). PTFs represent a low cost and easy technique to estimate soil hydraulic properties, to improve water management efficiency for the farmers

Changes in soil surface properties under simulated rainfall and the effect of surface roughness on runoff, infiltration and soil loss

Soil erosion by water is a result of detachment of particles or small aggregates from the soil surface followed by transport of the detached material. One of the elements that affects surface runoff and soil erosion is the soil surface roughness (SSR). Prior research reports that increasing SSR reduces generation of runoff and soil loss. In addition to that, it is widely reported that across-slope oriented roughness is better at controlling soil and water losses. However, to date there have been few studies into the effect of both magnitude and orientation of SSR on runoff, infiltration and soil erosion at the sub process level (i.e. by raindrop splash and overland flow), occurring simultaneously. In this study, the effects of up-down-slope oriented SSR (Treatment A), across-slope oriented SSR (Treatment B) and random SSR (Treatment C) were compared, along with a smooth surface (Treatment D). A moderate slope gradient of 10 %, a simulated rainfall intensity of 90 mm hr−1 and storm durations of 15 or 30 min were considered. The SSR was measured using the chain method, before and after the rainfall event. Images of the soil surface were taken using a hand-held laser scanner to monitor the effect of rainfall on the surface morphology. The outcome of this study shows that rainfall erosivity increases the SSR of the initially smooth surface, but decreases that of the initially rough surface, particularly in the random SSR treatment, where the decrease in SSR was 64 % of the pre-rainfall condition. This was due to the effects of raindrop impacts and overland flow. The random SSR treatment generated significantly more runoff and soil loss, and less infiltration than all other treatments (p < 0.001), but for raindrop splash erosion, there was no significant difference between random SSR and the other treatments. Contrary to expectations, the across-slope oriented SSR did not always reduce runoff and soil erosion compared to the up-down-slope orientation. This can be explained by degradation of surface microtopography by rainfall and runoff, as confirmed by the post-rainfall SSR measurements

Immunological impact of an additional early measles vaccine in Gambian children: responses to a boost at 3 years.

BACKGROUND: Measles vaccine in early infancy followed by a dose at 9 months of age protects against measles and enhances child survival through non-specific effects. Little is known of immune responses in the short or long term after booster doses. METHODS: Infants were randomized to receive measles vaccine at 9 months of age (group 1) or 4 and 9 months of age (group 2). Both groups received a boost at 36 months of age. T-cell effector and memory responses using IFN-γ ELIspot and cytokine assays and antibody titres using a haemagglutination-inhibition assay were compared at various times. RESULTS: Vaccination at 4 months of age elicited antibody and CD4 T-cell mediated immune responses .Two weeks after vaccination at 9 months of age group 2 had much higher antibody titres than group1 infants; cell-mediated effector responses were similar. At 36 months of age group 2 antibody titres exceeded protective levels but were 4-fold lower than group 1; effector and cytokine responses were similar. Re-vaccination resulted in similar rapid and high antibody titres in both groups (median 512); cellular immunity changed little. At 48 months of age group 2 antibody concentrations remained well above protective levels though 2-fold lower than group 1; T-cell memory was readily detectable and similar in both groups. CONCLUSIONS: An additional early measles vaccine given to children at 4 months of age induced a predominant CD4 T-cell response at 9 months and rapid development of high antibody concentrations after booster doses. However, antibody decayed faster in these children than in the group given primary vaccination at 9 months of age. Cellular responses after 9 months were generally insignificantly different

Integrated knowledge translation in population health intervention research: a case study of implementation and outcomes from a school-based project.

BACKGROUND: Integrated knowledge translation (IKT) is encouraged in population health intervention research (PHIR) to ensure the co-production of policy-relevant research, yet there is little published literature that reports its implementation and outcomes. The purpose of this study was to describe and evaluate the IKT approach used in a school-based PHIR project to understand how the research informed policy and practice and identify what influenced the IKT process. METHODS: A case study approach was used to provide an in-depth description of the IKT process and understand the co-production and application of research evidence. Data were collected through document review, a survey with all elementary school principals in the school board (n = 18) following dissemination of School Reports and interviews with the IKT research team (including two researchers and three knowledge users). RESULTS: Approximately half of the principals reported reading their School Report (52%) and almost all of these principals attributed the partial or full adoption, or implementation, of a new practice as a result of using the information (89%). Key themes related to the IKT process emerged across the interviews, including supportive relationships, role clarity, competing priorities and the complexities of population health interventions. CONCLUSIONS: The findings suggest that, while IKT can support policy and practice, it can be challenging to maintain engagement due to differing priorities and role ambiguity. Additional recognition, investment and research would enable better implementation of the approach, thereby bridging the gap between research, policy and practice

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Gold nanoparticle-linked analysis of carbohydrate–protein interactions, and polymeric inhibitors, using unlabelled proteins; easy measurements using a ‘simple’ digital camera

Gold nanoparticle-linked analysis of carbohydrate–protein interactions, and polymeric inhibitors, using unlabelled proteins; easy measurements using a ‘simple’ digital camer