LABORATORY DIAGNOSIS OF ACANTHAMOEBA KERATITIS USING THE CEPHEID SMARTCYCLER® II AND THE EFFECTS OF TOPICAL OPHTHALMIC DRUGS ON REAL-TIME PCR

Introduction: Acanthamoeba keratitis (AK) infection needs to be diagnosed definitively to optimize therapy in order to avoid possible visual impairment.Aims: 1) To optimize two noted Real-time PCR (RT-PCR) TaqMan methods (Rivière and Qvarnstrom) using the Cepheid SmartCycler® II system. 2) To identify potential inhibitory effects from topical drugs on RT-PCR. 3) To validate and compare the two assays using ocular clinical samples.Methods: 1) Primers and probes were optimized for both assays to detect genus-specific Acanthamoeba 18S rDNA. 2) Thirteen topical ophthalmic drugs were diluted to determine the level of inhibitory effect present. The lowest non-inhibitory concentrations were then used to determine RT-PCR amplification efficiency. 3) Excess clinical samples (139) were processed for culture and assayed by both assays on the SmartCycler® II and the results were compared. Results: 1) The Rivière RT-PCR plasmid DNA, cyst and trophozoite limits of detection and amplification efficiency were 10.13 copies/10μl, 0.7/300µl, 2.3/300µl, 94% respectively. The Qvarnstrom RT-PCR plasmid DNA, cyst and trophozoite limits of detection and amplification efficiency were 43.8 copies/10μl, 0.7/300µl, 2.3/300µl, 92% respectively. 2) Out of the thirteen topical drugs, the most noteworthy result was that of Polyhexamethylene biguanide (PHMB). The non-inhibitory dilution and RT-PCR efficiency were 1/2560 and 72.7%. 3) The results of the clinical validation indicated that 134/139 (96.4%) results correlated between the two assays of which 4/134 samples were culture negative but RT-PCR positive. Conclusions: The two RT-PCR assays were optimized successfully on the SmartCycler® II system with comparable results in detecting genus - specific Acanthamoeba DNA. In examining the effects of thirteen topical drugs on RT-PCR, PHMB was demonstrated to both inhibit the reaction at a high dilution and reduce amplification efficiency substantially. Ocular samples (139) were tested using both assays and results thus far indicate that both could be used to diagnose AK in the laboratory.Public health relevance: RT-PCR can be used to rapidly diagnose AK. Commencement of AK specific therapy earlier will substantially reduce the patients the pain and suffering. Also by examining the effects of topical ophthalmic drugs on RT-PCR, the potential for false negative results and result delays could be minimized

THE ADOPTION AND DIFFUSION OF LEVEL FIELDS AND BASINS

Strategic investments in agriculture often are lumpy and irreversible, with significant impacts on operating and fixed costs. Leveling cotton fields to zero slope in central Arizona is a strategic decision made by relatively younger farmers who are farming fine-textured soils in irrigation districts with higher expected water costs. The diffusion of the technology across the region between 1968-89 appears to be both a function of institutional changes (e.g., the Groundwater Management Act of 1980, the Central Arizona Project) and the long-run expected price changes induced by these new policies.Crop Production/Industries,

Increasing power for voxel-wise genome-wide association studies : the random field theory, least square kernel machines and fast permutation procedures

Imaging traits are thought to have more direct links to genetic variation than diagnostic measures based on cognitive or clinical assessments and provide a powerful substrate to examine the influence of genetics on human brains. Although imaging genetics has attracted growing attention and interest, most brain-wide genome-wide association studies focus on voxel-wise single-locus approaches, without taking advantage of the spatial information in images or combining the effect of multiple genetic variants. In this paper we present a fast implementation of voxel- and cluster-wise inferences based on the random field theory to fully use the spatial information in images. The approach is combined with a multi-locus model based on least square kernel machines to associate the joint effect of several single nucleotide polymorphisms (SNP) with imaging traits. A fast permutation procedure is also proposed which significantly reduces the number of permutations needed relative to the standard empirical method and provides accurate small p-value estimates based on parametric tail approximation. We explored the relation between 448,294 single nucleotide polymorphisms and 18,043 genes in 31,662 voxels of the entire brain across 740 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Structural MRI scans were analyzed using tensor-based morphometry (TBM) to compute 3D maps of regional brain volume differences compared to an average template image based on healthy elderly subjects. We find method to be more sensitive compared with voxel-wise single-locus approaches. A number of genes were identified as having significant associations with volumetric changes. The most associated gene was GRIN2B, which encodes the N-methyl-d-aspartate (NMDA) glutamate receptor NR2B subunit and affects both the parietal and temporal lobes in human brains. Its role in Alzheimer's disease has been widely acknowledged and studied, suggesting the validity of the approach. The various advantages over existing approaches indicate a great potential offered by this novel framework to detect genetic influences on human brains

Corticosteroids for the common cold

BACKGROUND: The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti‐inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. OBJECTIVES: To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). SELECTION CRITERIA: Randomised, double‐blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We were unable to perform meta‐analysis and instead present a narrative description of the available evidence. MAIN RESULTS: We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo‐controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single‐blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo‐controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. AUTHORS' CONCLUSIONS: Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double‐blind, placebo‐controlled trials in adults and children are required to answer this question

Evaporation of particle-stabilised emulsion sunscreen films

We recently showed (Binks et al., ACS Appl. Mater. Interfaces, 2016, DOI: 10.1021/acsami.6b02696) how evaporation of sunscreen films consisting of solutions of molecular UV filters leads to loss of UV light absorption and derived sun protection factor (SPF). In the present work, we investigate evaporation-induced effects for sunscreen films consisting of particle-stabilized emulsions containing a dissolved UV filter. The emulsions contained either droplets of propylene glycol (PG) in squalane (SQ), droplets of SQ in PG or droplets of decane in PG. In these different emulsion types, the SQ is involatile and shows no evaporation, the PG is volatile and evaporates relatively slowly, whereas the decane is relatively very volatile and evaporates quickly. We have measured the film mass and area, optical micrographs of the film structure, and the UV absorbance spectra during evaporation. For emulsion films containing the involatile SQ, evaporation of the PG causes collapse of the emulsion structure with some loss of specular UV absorbance due to light scattering. However, for these emulsions with droplets much larger than the wavelength of light, the light is scattered only at small forward angles so does not contribute to the diffuse absorbance and the film SPF. The UV filter remains soluble throughout the evaporation and thus the UV absorption by the filter and the SPF remain approximately constant. Both PG-in-SQ and SQ-in-PG films behave similarly and do not show area shrinkage by dewetting. In contrast, the decane-in-PG film shows rapid evaporative loss of the decane, followed by slower loss of the PG resulting in precipitation of the UV filter and film area shrinkage by dewetting which cause the UV absorbance and derived SPF to decrease. Measured UV spectra during evaporation are in reasonable agreement with spectra calculated using models discussed here

Spectrophotometry of thin films of light absorbing particles

Thin films of dispersions of light absorbing solid particles or emulsions containing a light absorbing solute all have a non-uniform distribution of light absorbing species throughout the sample volume. This results in non-uniform light absorption over the illuminated area which causes the optical absorbance, as measured using a conventional specular UV-vis spectrophotometer, to deviate from the Beer-Lambert relationship. We have developed a theoretical model to account for the absorbance properties of such films which are shown to depend on the size and volume fraction of the light absorbing particles plus other sample variables. We have compared model predictions with measured spectra for samples consisting of emulsions containing a dissolved light absorbing solute. Using no adjustable parameters, the model successfully predicts the behaviour of non-uniform, light absorbing emulsion films with varying values of droplet size, volume fraction and other parameters

A 17 degree of freedom anthropomorphic manipulator

A 17 axis anthropomorphic manipulator, providing coordinated control of two seven degree of freedom arms mounted on a three degree of freedom torso-waist assembly, is presented. This massively redundant telerobot, designated the Robotics Research K/B-2017 Dexterous Manipulator, employs a modular mechanism design with joint-mounted actuators based on brushless motors and harmonic drive gear reducers. Direct joint torque control at the servo level causes these high-output joint drives to behave like direct-drive actuators, facilitating the implementation of an effective impedance control scheme. The redundant, but conservative motion control system models the manipulator as a spring-loaded linkage with viscous damping and rotary inertia at each joint. This approach allows for real time, sensor-driven control of manipulator pose using a hierarchy of competing rules, or objective functions, to avoid unplanned collisions with objects in the workplace, to produce energy-efficient, graceful motion, to increase leverage, to control effective impedance at the tool or to favor overloaded joints

Cross-lagged associations between inter-parental relationship satisfaction and sibling relationship quality in families of children with intellectual disabilities

BACKGROUND: A family systems perspective hypothesises that the well-being of all family members is interconnected. However, limited research has examined the association between inter-parental conflict and sibling relationship quality in the context of intellectual disabilities. The aim of this study was to build on existing literature using longitudinal data, exploring potential (bi)directional associations between sibling relationship quality and inter-parental relationship satisfaction in families of children with intellectual disabilities. METHODS AND PROCEDURES: Primary caregivers (n = 223) of children with intellectual disabilities (M age at Wave 1 = 8.36 years, SD = 2.33) with at least one sibling (M age at Wave 1 = 8.45 years, SD = 2.47) completed the same online survey, 2 years 9 months apart. The survey measured inter-parental relationship quality and sibling relationship quality. A cross-lagged panel design was used to determine the directional associations between both subsystems. OUTCOMES AND RESULTS: The final autoregressive and cross-lagged models had good model fit. However, we found no evidence of any directional associations between sibling relationship quality and inter-parental relationship satisfaction. CONCLUSIONS AND IMPLICATIONS: The results from the current study contrast with previous literature, exhibiting the need for further research exploring factors associated with subsystem relationships in families of children with intellectual disabilities

Organisational interventions for improving wellbeing and reducing work-related stress in teachers [Review].

Background: The teaching profession is an occupation with a high prevalence of work-related stress. This may lead to sustained physical and mental health problems in teachers. It can also negatively affect the health, wellbeing and educational attainment of children, and impose a financial burden on the public budget in terms of teacher turnover and sickness absence. Most evaluated interventions for the wellbeing of teachers are directed at the individual level, and so do not tackle the causes of stress in the workplace. Organisational-level interventions are a potential avenue in this regard. Objectives: To evaluate the effectiveness of organisational interventions for improving wellbeing and reducing work-related stress in teachers. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, ASSIA, AEI, BEI, BiblioMap, DARE, DER, ERIC, IBSS, SSCI, Sociological Abstracts, a number of specialist occupational health databases, and a number of trial registers and grey literature sources from the inception of each database until January 2015. Selection criteria: Randomised controlled trials (RCTs), cluster-RCTs, and controlled before-and-after studies of organisational-level interventions for the wellbeing of teachers. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: Four studies met the inclusion criteria. They were three cluster-randomised controlled trials and one with a stepped-wedge design. Changing task characteristics One study with 961 teachers in eight schools compared a task-based organisational change intervention along with stress management training to no intervention. It found a small reduction at 12 months in 10 out of 14 of the subscales in the Occupational Stress Inventory, with a mean difference (MD) varying from -3.84 to 0.13, and a small increase in the Work Ability Index (MD 2.27; 95% confidence interval (CI) 1.64 to 2.90; 708 participants, low-quality evidence). Changing organisational characteristics@ Two studies compared teacher training combined with school-wide coaching support to no intervention. One study with 59 teachers in 43 schools found no significant effects on job-related anxiety (MD -0.25 95% CI -0.61 to 0.11, very low-quality evidence) or depression (MD -0.26 95% CI -0.57 to 0.05, very low-quality evidence) after 24 months. The other study with 77 teachers in 18 schools found no significant effects on the Maslach Burnout Inventory subscales (e.g. emotional exhaustion subscale: MD -0.05 95% CI -0.52 to 0.42, low-quality evidence) or the Teacher Perceived Emotional Ability subscales (e.g. regulating emotions subscale: MD 0.11 95% CI -0.11 to 0.33, low-quality evidence) after six months. Multi-component intervention: One study with 1102 teachers in 34 schools compared a multi-component intervention containing performance bonus, job promotion opportunities and mentoring support to a matched-comparison group consisting of 300 schools. It found moderately higher teacher retention rates (MD 11.50 95% CI 3.25 to 19.75 at 36 months follow-up, very low-quality evidence). However, the authors reported results only from one cohort out of four (eight schools), demonstrating a high risk of reporting bias. Authors’ conclusions: We found low-quality evidence that organisational interventions lead to improvements in teacher wellbeing and retention rates. We need further evaluation of the effects of organisational interventions for teacher wellbeing. These studies should follow a complex- interventions framework, use a cluster-rando