Double-blind Experiment Research Articles

The effect of a pressure vest on the behaviour, salivary cortisol and urine oxytocin of noise phobic dogs in a controlled test

Fear of loud noises is a common welfare problem in pet dogs. Commercial treatment vests have been tested on dogs to relieve noise phobia, and peripheral oxytocin has been suggested to be one of the stress-relieving mediators. The effect of vests has not, however, been tested in a controlled situation. We tested whether individually customized vests, have an effect on behaviour of severely noise phobic dogs in a double-blinded experiment, where dogs are exposed to loud noises. We also investigated the possible effect of pressure by using two types of vests; a deep pressure vest (DEEP, c. 10–12mmHg) and a light pressure vest (LIGHT, c. 2–3mmHg). In addition to behaviour, we studied if the pressure vest has an effect on urine oxytocin level and on saliva cortisol levels.A total of 28 dogs (2–11 years), both female (18) and male (10), were recruited via an ongoing study on the genetic background of noise sensitivity by the Finnish Canine Genetic Research Group. Each dog was tested three times either without vest (CONTROL) or with DEEP or LIGHT vests in a semi-randomized order. The dogś behaviour was video recorded for 6min, including three 2min intervals: pre-noise, noise (70–73dB firework sound) and recovery. Behavioural parameters included activity, body and tail postures, vocalization, and time spent near owner. Saliva samples were collected twice before and twice after the noise test. Urine samples for oxytocin analyses were collected when the deep pressure vest was first fitted: before dressing the dog and 30min later.The DEEP vest reduced the lying time of the dogs during the noise interval. During the noise interval total lying time with any vest correlated positively with saliva cortisol, measured after noise interval, indicating that the increased lying time was a sign of a higher stress level in the dogs. Wearing either vests increased the time the dogs spent near their owners during noise interval. Time spent near the owner when wearing the DEEP vest during the recovery interval correlated positively with the urine oxytocin. These results indicate oxytocin might be related to the doǵs tendency to seek owner support and the vests might effect this behaviour positively. We did not find a clear therapeutic effect of using pressure vests in noise phobic dogs. However, our results indicate the pressure vest might reduce the acute stress reaction and speed up the recovery after stress.

Control charts for monitoring accumulating adverse event count frequencies from single and multiple blinded trials.

Conventional practice monitors accumulating information about drug safety in terms of the numbers of adverse events reported from trials in a drug development program. Estimates of between-treatment adverse event risk differences can be obtained readily from unblinded trials with adjustment for differences among trials using conventional statistical methods. Recent regulatory guidelines require monitoring the cumulative frequency of adverse event reports to identify possible between-treatment adverse event risk differences without unblinding ongoing trials. Conventional statistical methods for assessing between-treatment adverse event risks cannot be applied when the trials are blinded. However, CUSUM charts can be used to monitor the accumulation of adverse event occurrences. CUSUM charts for monitoring adverse event occurrence in a Bayesian paradigm are based on assumptions about the process generating the adverse event counts in a trial as expressed by informative prior distributions. This article describes the construction of control charts for monitoring adverse event occurrence based on statistical models for the processes, characterizes their statistical properties, and describes how to construct useful prior distributions. Application of the approach to two adverse events of interest in a real trial gave nearly identical results for binomial and Poisson observed event count likelihoods. Copyright © 2016 John Wiley & Sons, Ltd.

Abstract PR482

Background & Objectives: Ultrasound (US) guided transversus abdominis plane (TAP) block is a proven postoperative analgesic technique after lower abdominal surgeries. Spread of drug in the TAP is an important consideration influencing the block. Addition of hyaluronidase to local anaesthetic,bupivacaine may improve quality of analgesia. Materials & Methods: US guided TAP block was performed before extubation on 60 consenting adult patients undergoing unilateral inguinal hernia repair under general anaesthesia. After randomization, 30 patients received bupivacaine 0.25% (19ml) with normal saline (1ml) (Group A) and 30 patients received bupivacaine 0.25% (19ml) with hyaluronidase 1500U (1ml) (Group B)with double blinding. Sample size of 30 each was based on assumption of 20% improvement in quality of blockade in Group B. Pain was assessed using numeric rating scale (NRS) at rest, movement and cough from 10th minute to 24 hours. Duration of analgesia, need for rescue analgesic and 24 hour tramadol consumption and others were noted. Results: Patients were comparable with respect to baseline characteristics. NRS on cough was low in Group B from 10th minute to 24 hours(P<0.05). NRS on movement was significantly low from 2nd to 24th hour(P<0.05) in group B. 24 hour tramadol consumption was comparable in both groups.Conclusion: The addition of hyaluronidase was associated with significant reduction of NRS at cough, and may be attributed to the improved quality of analgesia as a result of increased spread due to hyaluronidase.

Pediatric multiple sclerosis

Many disease-modifying therapies are currently available for adults with relapsing-remitting multiple sclerosis (MS) but none of them has been tested in pediatric MS in randomized placebo-controlled trials. At present, as suggested by observational studies and experts' guidelines, interferon-β and glatiramer acetate continue to be the standard first-line treatments for pediatric MS. Observational studies and some controlled unblinded trials have shown a positive effect of these meditations in reducing relapse rate and delaying disease progression, with an acceptable safety profile. The goal of this article is to provide an overview of current knowledge with regard to safety, tolerability, and efficacy of first-line treatment options for MS in the pediatric age group, with the aim of providing guidance for planning first-line treatment of MS in children and adolescents.

The effectiveness of computer-based spaced repetition in foreign language vocabulary instruction: a double-blind study

The purpose of the present paper is twofold; first, we present an empirical study evaluating the effectiveness of a novel CALL tool for foreign language vocabulary instruction based on spaced repetition of target vocabulary items. The study demonstrates that by spending an average of three minutes each day on automatically generated vocabulary activities, EFL students increased their long-term vocabulary retention rate three fold. Second, we demonstrate that the double-blind experiment design, which has become standard research practice in such extremely high-stakes fields as pharmacology and healthcare, has the potential of being successfully implemented in CALL research.

The Impact of Weight Labels on Body Image, Internalized Weight Stigma, Affect, Perceived Health, and Intended Weight Loss Behaviors in Normal-Weight and Overweight College Women.

To explore the psychological impact of weight labels. A double-blind experiment that randomly informed participants that they were "normal weight" or "overweight." Public university in Honolulu, Hawai'i. Normal-weight and overweight female undergraduates (N = 113). The Body Image States Scale, Stunkard Rating Scale, Weight Bias Internalization Scale, Positive and Negative Affect Schedule, General Health question from the 12-item Short Form Health Survey, modified version of the Weight Loss Methods Scale, and a manipulation check. A 2 × 2 between-subjects analysis of variance explored the main effects of the assigned weight label and actual weight and interactions between assigned weight label and actual weight. Significant main effects of the assigned weight label emerged on measures of body dissatisfaction, F(1, 109) = 12.40, p = .001, [Formula: see text] = 0.10, internalized weight stigma, F(1, 108) = 4.35, p = .039, [Formula: see text] = .04, and negative affect, F(1, 108) = 9.22, p = .003, [Formula: see text] = .08. Significant assigned weight label × actual weight interactions were found on measures of perceived body image, F(1, 109) = 6.29, p = .014, [Formula: see text] = .06, and perceived health, F(1, 109) = 4.18, p = .043, [Formula: see text] = .04. A weight label of "overweight" may have negative psychological consequences, particularly for overweight women.

Role of Epidemiology in Boicide Deaths in a Korean Law Suit

In the spring of 2011 in Korea, a cluster of pregnant women and children were admitted to intensive care units, and a case-control study charged by Korean Center for Disease Control revealed the association between rapidly progressing pulmonary fibrosis and humidifier biocides. Animal experiments soon identified the same pulmonary lesions as in humans, and then toxicity of humidifier biocides were evaluated for the first time. In 2015, a criminal charge was brought against the manufacturing companies for the negligence in the product safety and all the evidences of the causality for deaths from biocide exposure were brought on the table of the court. The companies are denying the causality itself, and causality in the diagnosis of humidifier disinfectant lung injury becomes the central issue of the dispute. The following issues were noted in the midst of the controversies between the prosecutors and the companies. Case definition in the case control study was challenged that the patients studied in the case control study do not have the same diseases, which may make the conclusion invalid. (misclassification) Errors in the differential diagnosis of patients can result in confounding, especially by viral infections. (confounding) Double blinding was not followed in the case control study. (information bias) In bringing these issues, it was noted that distinctions between general causality determination among multiple individuals versus specific causality determination for an individual were lost in the argument of linking errors of differential diagnosis in clinical medicine to the defects of epidemiology study. Another issue to note is the influence of foreign consultants, such as Gradient, in raising doubt about the results of academic studies that were published in the peer-reviewed journals. Three lessons that I learned from this experience are 1) the need to clarify how the assessment of causal association in epidemiology can be different from the clinical diagnosis, 2) any need of differences in the rigorousness of evidence of causality between criminal versus civil law suits, 3) the pros and cons in the replacement of domestic authoritative opinions with foreign consultations.

Melatonin as add-on treatment for epilepsy.

This is an updated version of the original Cochrane review published in Issue 6, 2012.Epilepsy is one of the most common chronic neurological disorders. Despite the plethora of antiepileptic drugs (AEDs) currently available, 30% of people continue having seizures. This group of people requires a more aggressive treatment, since monotherapy, the first choice scheme, fails to control seizures. Nevertheless, polytherapy often results in a number of unwanted effects, including neurological disturbances (somnolence, ataxia, dizziness), psychiatric and behavioural symptoms, and metabolic alteration (osteoporosis, inducement or inhibition of hepatic enzymes, etc.). The need for better tolerated AEDs is even more urgent in this group of people. Reports have suggested an antiepileptic role of melatonin with a good safety profile. To assess the efficacy and tolerability of melatonin as add-on treatment for epilepsy. For the latest update, we searched the Cochrane Epilepsy Group's Specialized Register (12 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 12 January 2016), and MEDLINE (Ovid, 11 January 2016). We searched the bibliographies of any identified study for further references. We handsearched selected journals and conference proceedings. We applied no language restrictions. In addition, we contacted melatonin manufacturers (i.e. Nathura) and original investigators to identify any unpublished studies. Randomized controlled trials; double, single, or unblinded trials; parallel group or cross-over studies. People with epilepsy regardless of age and gender, including children and adults with disabilities. Administration of melatonin as add-on treatment to any AED(s) compared to add-on placebo or no add-on treatment. Review authors independently selected trials for inclusion according to pre-defined criteria, extracted relevant data, and evaluated the methodological quality of trials. We assessed the following outcomes: at least 50% seizure reduction, seizure freedom, adverse events, and quality of life. We included six publications, with 125 participants (106 aged under 18 years). Two different comparisons were available: melatonin versus placebo and melatonin 5 mg versus melatonin 10 mg. Despite our primary intention, due to insufficient information on outcomes, we were unable to perform any meta-analyses, but summarized data narratively. Four studies were randomized, double-blind, cross-over, placebo-controlled trials and two were randomized, double-blind, parallel, placebo-controlled trials. Only two studies provided the exact number of seizures during the trial compared to the baseline: none of the participants with seizures during the trial had a change in seizure frequency compared with the baseline. Two studies systematically evaluated adverse effects (worsening of headache was reported in a child with migraine under melatonin treatment). Only one study systematically evaluated quality of life, showing no statistically significant improvement in quality of life in the add-on melatonin group. Included studies were of poor methodological quality, and did not systematically evaluate seizure frequency and adverse events, so that it was impossible to summarize data in a meta-analysis. It is not possible to draw any conclusion about the role of melatonin in reducing seizure frequency or improving quality of life in people with epilepsy.

The effects of resistance exercise in patients with knee osteoarthritis: a systematic review and meta-analysis

Objective: To analyze the effectiveness of resistance exercise in the treatment of knee osteoarthritis on pain, stiffness, and physical function. Design: Systematic review and meta-analysis of randomized controlled trials. Data sources: PubMed, Embase, Cochrane Central Register of Controlled Trials, the Web of Science, and Chinese Biomedical Literature Database were searched from the date of inception to August 2015. Methods: Trials comparing effects of resistance exercise intervention with either non-intervention or psycho-educational intervention were selected by two reviewers independently. The risk of bias was assessed and studies with similar outcomes were pooled using a fixed or random effects model. Results: Data from 17 randomized clinical trials including 1705 patients were integrated. The main source of methodological bias in the selected studies was lack of double blinding. The meta-analysis results suggested that resistance exercise training relieved pain (standard mean difference [SMD]: -0.43; 95% confidence interval [CI]: -0.57 to -0.29; P < 0.001), alleviated stiffness (SMD: -0.31; 95%: CI -0.56 to -0.05; P = 0.02), and improved physical function (SMD -0.53; 95% CI: -0.70 to -0.37; P < 0.001). Conclusion: Resistance exercise is beneficial in terms of reducing pain, alleviating stiffness, and improving physical function in patients with knee osteoarthritis.

The clinical importance of "bamboo joint-like appearance" on upper gastrointestinal endoscopy for the diagnosis of Crohn's disease.

Upper gastrointestinal (GI) lesions are frequently reported in Crohn's disease, in which the entire GI tract is affected. In these cases, erosive fissures regularly transversing folds that are longitudinally aligned along the lesser curvature of the gastric body and cardia are described as having a "bamboo joint-like appearance". We designed a blinded experiment in which upper GI imaging without a final diagnosis was checked by three observers to determine the usefulness of the bamboo joint-like appearance in the diagnosis of Crohn's disease. For the three observers, sensitivities of appearance were 30.5%, 56.9%, and 51.4%, while specificities were 99.6%, 98.5%, and 99.3%. Thus, the bamboo joint-like appearance was not useful for the identification of Crohn's disease patients. Nevertheless, patients exhibiting the bamboo joint-like appearance in upper GI imaging should undergo further examination due to the high probability of Crohn's disease.

Assessment of refinement of template-based models in CASP11.

CASP11 (the 11th Meeting on the Critical Assessment of Protein Structure Prediction) ran a blind experiment in the refinement of protein structure predictions, the fourth such experiment since CASP8. As with the previous experiments, the predictors were provided with one starting structure from the server models of each of a selected set of template-based modeling targets and asked to refine the coordinates of the starting structure toward native. We assessed the refined structures with the Z-scores of the standard CASP measures, which compare the model-target similarities of the models from all the predictors. Furthermore, we assessed the refined structures with "relative measures," which compare the improvement in accuracy of each model with respect to the starting structure. The latter provides an assessment of the extent to which each predictor group is able to improve the starting structures toward native. We utilized heat maps to display improvements in the Calpha-Calpha distance matrix for each model. The heat maps labeled with each element of secondary structure helped us to identify regions of refinement toward native in each model. Most positively scoring models show modest improvements in multiple regions of the structure, while in some models we were able to identify significant repositioning of N/C-terminal segments and internal elements of secondary structure. The best groups were able to improve more than 70% of the targets from the starting models, and by an average of 3-5% in the standard CASP measures. Proteins 2016; 84(Suppl 1):260-281. © 2016 Wiley Periodicals, Inc.

The outcome of decompression alone for lumbar spinal stenosis with degenerative spondylolisthesis.

Lumbar spinal stenosis in the presence of degenerative spondylolisthesis is generally treated by means of surgery. The role of lumbar decompression without fusion is not clear. Therefore, the aim of this study was to assess whether patients who undergo decompression alone have a favourable outcome without the need for a subsequent fusion. This is a prospective cohort study with single blinding of 83 consecutive patients with lumbar stenosis and degenerative spondylolisthesis treated by decompression, without fusion, using a spinous process osteotomy. Blinded observers collected pre- and post-operative Oswestry Disability Index (ODI), EuroQol Five Dimensions (EQ-5D), and visual analogue scale (VAS) for back and leg pain scores prospectively. Failures for this study were those patients who required a subsequent lumbar fusion procedure at the decompressed levels. Statistical analysis was performed using paired t test and Mann-Whitney test. There were 36 males and 47 females with a mean age of 66years (range 35-82). The mean follow-up was 36months (range 19-48months). The mean pre-operative ODI, EQ-5D, and VAS scores were 52 [standard deviation (SD) 18], 0.25 (SD 0.30), and 61 (SD 22), respectively. All mean scores improved post-operatively to 38 (SD 23), 0.54 (SD 0.34) and 36 (SD 27), respectively. There was a statistically significant improvement in all scores (p≤0.0001). Nine patients (11%) required a subsequent fusion procedure and five patients (6%) required revision decompression surgery alone. Our study's results show that a lumbar decompression procedure without arthrodesis in a consecutive cohort of patients with lumbar spinal stenosis with degenerative spondylolisthesis had a significant post-operative improvement in ODI, EQ-5D, and VAS. The rate of post-operative instability and subsequent fusion is not high. Only one in 10 patients in this group ended up needing a subsequent fusion at a mean follow-up of 36months, indicating that fusion is not always necessary in these patients.

Teaching a lay theory before college narrows achievement gaps at scale

Previous experiments have shown that college students benefit when they understand that challenges in the transition to college are common and improvable and, thus, that early struggles need not portend a permanent lack of belonging or potential. Could such an approach-called a lay theory intervention-be effective before college matriculation? Could this strategy reduce a portion of racial, ethnic, and socioeconomic achievement gaps for entire institutions? Three double-blind experiments tested this possibility. Ninety percent of first-year college students from three institutions were randomly assigned to complete single-session, online lay theory or control materials before matriculation (n > 9,500). The lay theory interventions raised first-year full-time college enrollment among students from socially and economically disadvantaged backgrounds exiting a high-performing charter high school network or entering a public flagship university (experiments 1 and 2) and, at a selective private university, raised disadvantaged students' cumulative first-year grade point average (experiment 3). These gains correspond to 31-40% reductions of the raw (unadjusted) institutional achievement gaps between students from disadvantaged and nondisadvantaged backgrounds at those institutions. Further, follow-up surveys suggest that the interventions improved disadvantaged students' overall college experiences, promoting use of student support services and the development of friendship networks and mentor relationships. This research therefore provides a basis for further tests of the generalizability of preparatory lay theories interventions and of their potential to reduce social inequality and improve other major life transitions.

From painkiller to empathy killer: acetaminophen (paracetamol) reduces empathy for pain

Simulation theories of empathy hypothesize that empathizing with others' pain shares some common psychological computations with the processing of one's own pain. Support for this perspective has largely relied on functional neuroimaging evidence of an overlap between activations during the experience of physical pain and empathy for other people's pain. Here, we extend the functional overlap perspective to the neurochemical level and test whether a common physical painkiller, acetaminophen (paracetamol), can reduce empathy for another's pain. In two double-blind placebo-controlled experiments, participants rated perceived pain, personal distress and empathic concern in response to reading scenarios about another's physical or social pain, witnessing ostracism in the lab, or visualizing another study participant receiving painful noise blasts. As hypothesized, acetaminophen reduced empathy in response to others' pain. Acetaminophen also reduced the unpleasantness of noise blasts delivered to the participant, which mediated acetaminophen's effects on empathy. Together, these findings suggest that the physical painkiller acetaminophen reduces empathy for pain and provide a new perspective on the neurochemical bases of empathy. Because empathy regulates prosocial and antisocial behavior, these drug-induced reductions in empathy raise concerns about the broader social side effects of acetaminophen, which is taken by almost a quarter of adults in the United States each week.

Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models.

The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.

3Drefine: an interactive web server for efficient protein structure refinement.

3Drefine is an interactive web server for consistent and computationally efficient protein structure refinement with the capability to perform web-based statistical and visual analysis. The 3Drefine refinement protocol utilizes iterative optimization of hydrogen bonding network combined with atomic-level energy minimization on the optimized model using a composite physics and knowledge-based force fields for efficient protein structure refinement. The method has been extensively evaluated on blind CASP experiments as well as on large-scale and diverse benchmark datasets and exhibits consistent improvement over the initial structure in both global and local structural quality measures. The 3Drefine web server allows for convenient protein structure refinement through a text or file input submission, email notification, provided example submission and is freely available without any registration requirement. The server also provides comprehensive analysis of submissions through various energy and statistical feedback and interactive visualization of multiple refined models through the JSmol applet that is equipped with numerous protein model analysis tools. The web server has been extensively tested and used by many users. As a result, the 3Drefine web server conveniently provides a useful tool easily accessible to the community. The 3Drefine web server has been made publicly available at the URL: http://sysbio.rnet.missouri.edu/3Drefine/.

Generating, Maintaining, and Exploiting Diversity in a Memetic Algorithm for Protein Structure Prediction.

Computational approaches to de novo protein tertiary structure prediction, including those based on the preeminent "fragment-assembly" technique, have failed to scale up fully to larger proteins (on the order of 100 residues and above). A number of limiting factors are thought to contribute to the scaling problem over and above the simple combinatorial explosion, but the key ones relate to the lack of exploration of properly diverse protein folds, and to an acute form of "deception" in the energy function, whereby low-energy conformations do not reliably equate with native structures. In this article, solutions to both of these problems are investigated through a multistage memetic algorithm incorporating the successful Rosetta method as a local search routine. We found that specialised genetic operators significantly add to structural diversity and that this translates well to reaching low energies. The use of a generalised stochastic ranking procedure for selection enables the memetic algorithm to handle and traverse deep energy wells that can be considered deceptive, which further adds to the ability of the algorithm to obtain a much-improved diversity of folds. The results should translate to a tangible improvement in the performance of protein structure prediction algorithms in blind experiments such as CASP, and potentially to a further step towards the more challenging problem of predicting the three-dimensional shape of large proteins.

The Effects of Exogenous Testosterone on Men’s Moral Decision-Making

Correlational research has linked testosterone (T) to moral reasoning, such that individuals high in T respond to moral dilemmas in a more utilitarian manner (Carney and Mason 2010). In the present study, 30 male undergraduates completed baseline measures of T, psychopathic traits, and digit-ratio (2D:4D) and were subsequently administered 150 mg of testosterone or placebo in a double-blind within-subjects experiment meant to explore a potential causal influence of T on moral decision-making. Following drug administration, participants rated their agreement with a set of incidental and instrumental moral dilemmas, the total of which provided an index of the participant’s utilitarian decision-making on that testing day. Results revealed a significant drug × type of dilemma interaction. Post-hoc analyses revealed that T administration was associated with increased utilitarian behavior within incidental moral dilemmas, but with decreased utilitarian decision-making in instrumental dilemmas, although neither trend was statistically-significant. The interpersonal/affective facet (i.e., Factor 1) of psychopathy was positively correlated with utilitarian responses. No effects were found for baseline testosterone or digit ratio. Potential reasons underlying the effect of T decreasing utilitarianism in incidental dilemmas, as well as future directions for research in this area, are discussed.

Size-selective analyte detection with a Young interferometer sensor using multiple wavelengths.

We present a method to discriminate between analytes based on their size using multiple wavelengths in a Young interferometer. We measured the response of two wavelengths when adding 85 nm beads (representing specific binding), protein A (representing non-specific binding) and D-glucose (inducing a bulk change) to our sensor. Next, the measurements are analysed using a approach based on theoretical analysis, and a ratio-based analysis approach to discriminate between bulk changes and the binding of the different sized substances. Moreover, we were able to discriminate binding of 85 nm beads from binding of protein A (~2 nm) in a blind experiment using the ratio-based approach. This can for example be used to discriminate specific analyte binding of larger particles from non-specific binding of smaller particles. Therefore, we believe that by adding size-selectivity we can strongly improve the performance of the Young interferometer sensor and integrated optical interferometric sensors in general.

Melatonin as add-on treatment for epilepsy.

This is an updated version of the original Cochrane review published in Issue 6, 2012.Epilepsy is one of the most common chronic neurological disorders. Despite the plethora of antiepileptic drugs (AEDs) currently available, 30% of people continue having seizures. This group of people requires a more aggressive treatment, since monotherapy, the first choice scheme, fails to control seizures. Nevertheless, polytherapy often results in a number of unwanted effects, including neurological disturbances (somnolence, ataxia, dizziness), psychiatric and behavioural symptoms, and metabolic alteration (osteoporosis, inducement or inhibition of hepatic enzymes, etc.). The need for better tolerated AEDs is even more urgent in this group of people. Reports have suggested an antiepileptic role of melatonin with a good safety profile. To assess the efficacy and tolerability of melatonin as add-on treatment for epilepsy. For the latest update, we searched the Cochrane Epilepsy Group's Specialized Register (12 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 12 January 2016), and MEDLINE (Ovid, 11 January 2016). We searched the bibliographies of any identified study for further references. We handsearched selected journals and conference proceedings. We applied no language restrictions. In addition, we contacted melatonin manufacturers (i.e. Nathura) and original investigators to identify any unpublished studies. Randomized controlled trials; double, single, or unblinded trials; parallel group or cross-over studies. People with epilepsy regardless of age and gender, including children and adults with disabilities. Administration of melatonin as add-on treatment to any AED(s) compared to add-on placebo or no add-on treatment. Review authors independently selected trials for inclusion according to pre-defined criteria, extracted relevant data, and evaluated the methodological quality of trials. We assessed the following outcomes: at least 50% seizure reduction, seizure freedom, adverse events, and quality of life. We included six publications, with 125 participants (106 aged under 18 years). Two different comparisons were available: melatonin versus placebo and melatonin 5 mg versus melatonin 10 mg. Despite our primary intention, due to insufficient information on outcomes, we were unable to perform any meta-analyses, but summarized data narratively. Four studies were randomized, double-blind, cross-over, placebo-controlled trials and two were randomized, double-blind, parallel, placebo-controlled trials. Only two studies provided the exact number of seizures during the trial compared to the baseline: none of the participants with seizures during the trial had a change in seizure frequency compared with the baseline. Two studies systematically evaluated adverse effects (worsening of headache was reported in a child with migraine under melatonin treatment). Only one study systematically evaluated quality of life, showing no statistically significant improvement in quality of life in the add-on melatonin group. Included studies were of poor methodological quality, and did not systematically evaluate seizure frequency and adverse events, so that it was impossible to summarize data in a meta-analysis. It is not possible to draw any conclusion about the role of melatonin in reducing seizure frequency or improving quality of life in people with epilepsy.