Double-blind Experiment Research Articles

Double-blind validation of alternative wild bee identification techniques: DNA metabarcoding and in vivo determination in the field

Over the past few decades, several investigations around the globe have reported alarming declines in the abundance and diversity of bee species. The success of effective conservation strategies targeting these important pollinators relies heavily on accurate biodiversity assessments. The shortage of taxonomic experts and the escalation of the ongoing biodiversity crisis call for the development of alternative identification tools to implement efficient monitoring programs. The validation of such techniques is crucial to ensure that they provide results comparable to those of traditional morphotaxonomy. Here we performed two double-blind experiments to evaluate the accuracy of a pair of new techniques used for wild bee identification: DNA metabarcoding and in vivo identification in the field. The methods were tested on sets of wild bees from Germany and their results compared against evaluations done by panels of bee experts using traditional morphotaxonomy. On average the congruency of species identification between metabarcoding and morphotaxonomy was 88.98% across samples (N = 10), while in vivo identification and morphotaxonomy were 91.81% congruent (N = 7) for bees considered feasible for in vivo identification in the field. Traditional morphotaxonomy showed similar congruencies when compared to itself: 93.65% in the metabarcoding study and 92.96% in the in vivo study. Overall, these results support both new methods as viable alternatives to traditional microscopy-based assessment, with neither method being error-free. Metabarcoding provides a suitable option to analyze large numbers of specimens in the absence of highly trained taxonomic experts, while in vivo identification is recommended for repeated long-term monitoring, and when working in areas where the sampling of individuals could threaten local populations of endangered wild bee species. Further research is still needed to explore the potential of both techniques for conservation management and wildlife monitoring, as well as to overcome their current limitations as taxonomic tools.

Negative mood mind wandering and unsafe driving in young male drivers

ObjectiveRoad traffic crash fatalities disproportionately affect young male drivers. Driver distraction is a leading contributor to crashes. Mind wandering (MW) is a prevalent form of driver distraction that is linked to certain unsafe driving behaviours that are associated with increased crash risk (e.g., faster driving). Negative mood can lead to MW, and thus may represent a causal pathway to MW-related unsafe driving. This preliminary pre-post (T1, T2), randomized, controlled, single-blinded experiment tested whether negative mood, compared to neutral mood, increases MW while driving as well as unsafe driving and emotional arousal during MW. It also tested the moderating contribution of trait rumination and inhibitory control to this proposed causal pathway. MethodsForty healthy male drivers aged 20 to 24 were randomly allocated to a negative or neutral mood manipulation involving deception. Individual differences in trait rumination and inhibitory control were measured at T1. At T1 and T2, participants drove in a driving simulator measuring driving speed, headway distance, steering behaviour, and overtaking. Heart rate and thought probes during simulation measured emotional arousal and MW, respectively. ResultsNegative mood exposure led to more MW while driving (Odds Ratio = 1.79, p = .022). Trait rumination positively moderated the relationship between negative mood and MW (Odds Ratio = 2.11, p = .002). Negative versus neutral mood exposure led to increases in headway variability (Cohen’s d = 1.46, p = .026) and steering reversals (Rate Ratio = 1.33, p = .032) during MW relative to focused driving. Between-group differences in emotional arousal were not significant. ConclusionResults support a causal pathway from negative mood to unsafe driving via MW, including the moderating contribution of trait rumination. If replicated, these preliminary findings may inform the development of interventions targeting this potential crash-risk pathway in vulnerable young driver subgroups.

Acoustic coupling pads for the control of ultrasound neuromodulation exposure

We have developed acoustic coupling pads that facilitate single-blind and double-blind neuromodulation experiments by selectively transmitting ultrasound without affecting the audible sound. The pads were made from a skin-safe two-part silicone with little to no ultrasonic attenuation, that also provided the necessary acoustic properties, stability and flexibility. To inhibit the transmission of ultrasound, a foam disk was imbedded into the pad during the manufacturing process. The design goal for acoustic attenuation was −40 dB. 20 sets of transmit pads and non-transmit pads were fabricated. Acoustic transmission loss was measured in a water tank with a 60 mm diameter, 80 mm focus circular disk transducer operated at 650 kHz and a standard hydrophone (Reson TC4038). Transmit pads had an average of −0.4 dB loss; non-transmit pads met the required −40 dB loss (average: −47.4 dB). An operator experienced with ultrasound treatments was unable to distinguish them by visual inspection or casual physical manipulation. An experienced subject exposed to a typical treatment regimen was not able to distinguish any audible difference. The acoustic coupling pads create identical testing situations for single-blind and double-blind studies for neuromodulation treatments so that neither the patient nor the operator administering the treatment can distinguish which patient group received the ultrasound treatment and which did not.

Knowledge distillation driven instance segmentation for grading prostate cancer

Prostate cancer (PCa) is one of the deadliest cancers in men, and identifying cancerous tissue patterns at an early stage can assist clinicians in timely treating the PCa spread. Many researchers have developed deep learning systems for mass-screening PCa. These systems, however, are commonly trained with well-annotated datasets in order to produce accurate results. Obtaining such data for training is often time and resource-demanding in clinical settings and can result in compromised screening performance. To address these limitations, we present a novel knowledge distillation-based instance segmentation scheme that allows conventional semantic segmentation models to perform instance-aware segmentation to extract stroma, benign, and the cancerous prostate tissues from the whole slide images (WSI) with incremental few-shot training. The extracted tissues are then used to compute majority and minority Gleason scores, which, afterward, are used in grading the PCa as per the clinical standards. The proposed scheme has been thoroughly tested on two datasets, containing around 10,516 and 11,000 WSI scans, respectively. Across both datasets, the proposed scheme outperforms state-of-the-art methods by 2.01% and 4.45%, respectively, in terms of the mean IoU score for identifying prostate tissues, and 10.73% and 11.42% in terms of F1 score for grading PCa according to the clinical standards. Furthermore, the applicability of the proposed scheme is tested under a blind experiment with a panel of expert pathologists, where it achieved a statistically significant Pearson correlation of 0.9192 and 0.8984 with the clinicians’ grading.

Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children.

Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children.

The Feasibility of Early Alzheimer's Disease Diagnosis Using a Neural Network Hybrid Platform.

Early diagnosis of Alzheimer’s Disease (AD) is critical for disease prevention and cure. However, currently, techniques with the required high sensitivity and specificity are lacking. Recently, with the advances and increased accessibility of data analysis tools, such as machine learning, research efforts have increasingly focused on using these computational methods to solve this challenge. Here, we demonstrate a convolutional neural network (CNN)-based AD diagnosis approach using the surface-enhanced Raman spectroscopy (SERS) fingerprints of human cerebrospinal fluid (CSF). SERS and CNN were combined for biomarker detection to analyze disease-associated biochemical changes in the CSF. We achieved very high reproducibility in double-blind experiments for testing the feasibility of our system on human samples. We achieved an overall accuracy of 92% (100% for normal individuals and 88.9% for AD individuals) based on the clinical diagnosis. Further, we observed an excellent correlation coefficient between our test score and the Clinical Dementia Rating (CDR) score. Our findings offer a substantial indication of the feasibility of detecting AD biomarkers using the innovative combination of SERS and machine learning. We are hoping that this will serve as an incentive for future research in the field.

Disposable and low-cost pen-like sensor incorporating nucleic-acid amplification based lateral-flow assay for at-home tests of communicable pathogens

Rapid at-home test is a good alternative to the gold standard quantitative polymerase chain reaction (qPCR) for early identification and management of infected individuals in pandemic. However, the currently available at-home rapid antigen kits and nucleic acid tests (NATs) are prone to false results. Although some CRISPR-mediated NATs enhanced accuracy, long turnaround time (ca. 1 h) and aerosol contamination due to additional open-lid reaction hinder its applicability for self-tests. Moreover, the accuracy of at-home NATs is also impacted by interference of sample matrix due to lack of sample purification. Here we report a Fast, Low-cost, Aerosol contamination-free and Sensitive molecular assay for at-Home tests of communicable pathogens (FLASH) incorporating oLAMP, a recently reported isothermal and target-specific NATs by our group, and a visible lateral-flow readout. The integrated platform enabled sample-to-result SARS-CoV-2 RNA detection in 20–30 min achieving a sensitivity of 0.5 copies/μL in a blinded experiment with a high accuracy comparable with the qPCR. Its prototype consists of two disposable pen-like instruments for single-step sample preparation and contamination-free NATs, respectively. The simplified workflow of the FLASH enabled detection to be readily conducted by untrained users for at-home tests. All in all, the FLASH prototype demonstrates itself to be a promising home-use assay platform for effective mitigation of the pandemic.

Fingernail electron paramagnetic resonance dosimetry protocol for localized hand exposure accident

Exposure to ionizing radiation induces free radicals in human nails. These free radicals generate a radiation-induced signal (RIS) in electron paramagnetic resonance (EPR) spectroscopy. Compared with the RIS of tooth enamel samples, that in human nails is more affected by moisture and heat, but has the advantages of being sensitive to radiation and easy to collect. The fingernail as a biological sample is applicable in retrospective dosimetry in cases of localized hand exposure accidents. In this study, the dosimetric characteristics of fingernails were analyzed in fingernail clippings collected from Korean donors. The dose response, fading of radiation-induced and mechanically induced signals, treatment method for evaluation of background signal, minimum detectable dose, and minimum detectable mass were investigated to propose a fingernail-EPR dosimetry protocol. In addition, to validate the practicality of the protocol, blind and field experiments were performed in the laboratory and a non-destructive testing facility. The relative biases in the dose assessment result of the blind and field experiments were 8.43% and 21.68% on average between the reference and reconstructed doses. The results of this study suggest that fingernail-EPR dosimetry can be a useful method for the application of retrospective dosimetry in cases of radiological accidents.

Paper Device Combining CRISPR/Cas12a and Reverse-Transcription Loop-Mediated Isothermal Amplification for SARS-CoV-2 Detection in Wastewater.

Wastewater-based surveillance of the COVID-19 pandemic holds great promise; however, a point-of-use detection method for SARS-CoV-2 in wastewater is lacking. Here, a portable paper device based on CRISPR/Cas12a and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with excellent sensitivity and specificity was developed for SARS-CoV-2 detection in wastewater. Three primer sets of RT-LAMP and guide RNAs (gRNAs) that could lead Cas12a to recognize target genes via base pairing were used to perform the high-fidelity RT-LAMP to detect the N, E, and S genes of SARS-CoV-2. Due to the trans-cleavage activity of CRISPR/Cas12a after high-fidelity amplicon recognition, carboxyfluorescein-ssDNA-Black Hole Quencher-1 and carboxyfluorescein-ssDNA-biotin probes were adopted to realize different visualization pathways via a fluorescence or lateral flow analysis, respectively. The reactions were integrated into a paper device for simultaneously detecting the N, E, and S genes with limits of detection (LODs) of 25, 310, and 10 copies/mL, respectively. The device achieved a semiquantitative analysis from 0 to 310 copies/mL due to the different LODs of the three genes. Blind experiments demonstrated that the device was suitable for wastewater analysis with 97.7% sensitivity and 82% semiquantitative accuracy. This is the first semiquantitative endpoint detection of SARS-CoV-2 in wastewater via different LODs, demonstrating a promising point-of-use method for wastewater-based surveillance.

Information fields of written texts protect cells from oxidative damage and accelerate repair

ObjectiveWritten words demonstrated specific effects on biochemical measures and cell growth in cultured mammalian cells in previous study. We examined the protection and reparative effects of Chinese texts with positive meaning and the word "Buddha" on oxidative-damaged cells, with the goal of exploring the therapeutic effect of such characters. MethodsThe human embryonic kidney cell line HEK293T was utilized, with the oxidative- damaged cell model produced by hydrogen peroxide (H2O2). Double-blind experiments were set up to ensure all operators involved in the experiments did not know the contents of the texts in envelopes. Petri-dishes (9 plates) containing oxidative-damaged cells were selected randomly for three controls, three treatments by texts with positive meaning, and another three treatment by the word “Buddha”. Cells were sub-sampled at 3 h and 24 h to examine growth and mitochondrial functions. All data are expressed relative to the controls. ResultsCompared with the control group, mitochondrial functions were enhanced as evidenced by increased adenosine triphosphate (ATP) levels, accompanied by the significant improvement in cell growth rate for the groups treated by positive texts and the word “Buddha”. Reactive oxygen species (ROS) levels were decreased significantly in positive texts treatment, which suggested that the antioxidant capacity of cells was also improved. ConclusionsThis study revealed that certain texts can potentially offer protection and accelerate the cellular repair for oxidative-damaged cells.

Species-specific identification of Pseudomonas based on 16S–23S rRNA gene internal transcribed spacer (ITS) and its combined application with next-generation sequencing

BackgroundPseudomonas species are widely distributed in the human body, animals, plants, soil, fresh water, seawater, etc. Pseudomonas aeruginosa is one of the main pathogens involved in nosocomial infections. It can cause endocarditis, empyema, meningitis, septicaemia and even death. However, the Pseudomonas classification system is currently inadequate and not well established.ResultsIn this study, the whole genomes of 103 Pseudomonas strains belonging to 62 species available in GenBank were collected and the specificity of the 16S–23S ribosomal RNA internal transcribed spacer (ITS) sequence was analysed. Secondary structures of ITS transcripts determining where the diversity bases were located were predicted. The alignment results using BLAST indicated that the ITS sequence is specific for most species in the genus. The remaining species were identified by additional frequency analyses based on BLAST results. A double-blind experiment where 200 ITS sequences were randomly selected indicated that this method could identify Pseudomonas species with 100% sensitivity and specificity. In addition, we applied a universal primer to amplify the Pseudomonas ITS of DNA extracts from fish samples with next-generation sequencing. The ITS analysis results were utilized to species-specifically identify the proportion of Pseudomonas species in the samples.ConclusionsThe present study developed a species-specific method identification and classification of Pseudomonas based on ITS sequences combined NGS. The method showed its potential application in other genera.

Effectiveness of autogenic drainage Vs incentive spirometry in intensive care unit

Background: Intensive Care Units are the most demanding place in hospital setup as they provide clear and fair information to patients and family. Physical therapy involves several techniques that plays significant role in intensive care unit, focusing on goals like recruit lung volume, improving ventilation perfusion, improving oxygenation, promoting secretion clearance. Studies has been conducted regarding effectiveness of Incentive spirometry and autogenic drainage but there was very low data regarding Comparison of Incentive spirometry and autogenic drainage. Objective: The aim of this study was to find the effectiveness of Incentive spirometry vs Autogenic Drainage in Intensive Care Unit. Methodology: This was an experimental study conducted in LIAQUAT NATIONAL HOSPITAL from MAY-NOV. Systematic sampling technique was used, single blinding was done. Samples were allocated into 2 groups. One group receiving autogenic drainage while other receiving incentive spirometry. Total number of 10 sessions were given to each group. Pulmonary function testing and ABGs were used as assessment tools, consent form was signed by participants. Data was analyzed using SPSS 22 Version. Result: The result of autogenic drainage measuring expiratory reserve volume showed that before autogenic drainage the mean of the group was 748+-182.8 and after session of 7 days there was significant increase of expiratory reserve volume as well which is 864+-207.9, Thus the result of this study showed that Autogenic Drainage was statically significant in improving expiratory reserve volume. Conclusion: Result of this study showed Autogenic Drainage was more effective than Incentive Spirometry in improving expiratory reserve volume. Apart from this, Physiotherapists should use these techniques more in ICUs for better results and to reduce mortality rate.

THE EFFECTS OF CREATINE SUPPLEMENTATION ON SINGLE AND INTERMITTENT ANAEROBIC EXERCISES AND BODY COMPOSITION DURING REDUCED TRAINING IN SOCCER PLAYERS

Abstract: BACKGROUNDː Several studies have examined the effects of creatine supplementation in adult athletes in season or pre-season preparation. However, few studies have examined the effects of creatine supplementation in adolescent soccer players during reduced training in an off-season. OBJECTIVE: The aim of the study was to examine the effects of short-term creatine monohydrate supplementation on the anaerobic performance and body composition in adolescent soccer players during reduced training in an off-season. METHODSː Using a double-blind experiment design, 16 soccer players (aged 18.0 ± 0.8 yr) were randomly assigned to 5 days of either 20 g . day-1 creatine monohydrate (Cr) or placebo supplementation. One day before and a day after the supplementation, participants completed squat and countermovement jumps (SJ, CMJ), 10-m running sprint, 6-s single cycling sprint (CST), an intermittent anaerobic test on a bicycle ergometer (10 x 6s, IAnTBE) and measurement of body composition. RESULTSː Cr supplementation had no significant effect (p > .05) on any performance test. However, effect size values indicated medium or small clinical significance in SJ (d = 0.59), CST (6-s power, d = 0.50; peak power, d = 0.48) and IAnTBE (best peak power, d = 0.44; post-exercise blood lactate concentration, d = - 0.59; fatigue index, d = - 0.28 ). Relative to the placebo, Cr supplementation resulted in a significant increase in body weight (BW) (p = .015). CONCLUSIONSː The results of the study suggest that short-term Cr supplementation administered to adolescent soccer players during their off-season significantly increase body weight and could have small/medium clinical significance effect on improve lower-body maximal anaerobic power output and power output recovery during maximal intermittent exercise. The study also confirms that Cr supplementation is safe and without side effects for adolescent athletes.

A Bayesian Modeling Approach to Examine the Role of Testosterone Administration on the Endowment Effect and Risk-Taking

Financial risk-taking and loss aversion are multifaceted phenomena that are the focus of neuroscience, psychology, and economics research. A growing number of studies highlighted the role of hormones (particularly of testosterone) on socio-economic decision-making. However, the effects of testosterone on risk-taking under framing and consumer-based choices and preferences are inconclusive. We investigated the effects of 100 mg testosterone administration on aspects of decision-making within the Prospect Theory framework which is the most used descriptive model of decision-making under risk. We assessed risk-taking under framing and the endowment effect (effect of possession) using Bayesian modeling. Forty men participated in this double-blind placebo-controlled fully-randomized cross-over experiment and performed two tasks. One was a risk-taking task with binary choices under positive and negative framing associated with different probabilities. In the second task participants had to bid money for hedonic and utilitarian items. We observed a significant increase in serum testosterone concentrations after transdermal application. Compared to placebo, testosterone administration increased risk-taking under the positive framing (very large effect size) and decreased under the negative framing (moderate to small). The sensitivity to gain was positive in each framing. Our model showed that decision-making is jointly influenced by testosterone and the trade-off between gains and losses. However, while the endowment effect was more pronounced for hedonic than for utilitarian items, the effect was independent of testosterone. The findings provide novel information on the complex modulatory role of testosterone on risk-taking within the framework of prospect theory and shed light on mechanisms of behavioral economic biases. The proposed models of effects of individual differences in testosterone on risk-taking could be used as predictive models for reference-depended behavior under positive and negative framing with low and high probabilities.

Coronal Movement during Flexion and Extension of Knee Joints.

Objective There are variabilities in the distance between the tibial tuberosity and the trochlear groove. The knee angle needs to be considered when talking about patellofemoral instability. Methods This retrospective study analyses the MRI images of knee angles from 0 and 30 degrees in the patella dislocation group (20 cases) and in the control group (20 cases) from Dec 2017 to Dec 2019. Two experienced orthopedic physicians separately measure the study with a blind experiment method. Results The TT-TG data of the patella dislocation group and control group are 17.88 ± 3.40 mm and 13.31 ± 3.01 mm when the knee angle is 0, which indicates a difference with statistical significance (P < 0.01). The TT-TG data of the patella dislocation group and control group are 11.51 ± 3.60 mm and 7.40 ± 1.93 mm when the knee angle is at 30 degrees, indicating a statistically significant difference (P < 0.01). Also, the TT-TG data of both the patella dislocation group and control group have statistically significant differences within different knee angles of the same group (P < 0.01). The differences of TT-TG are 6.36 ± 2.43 mm and 5.92 ± 1.65 mm when the knee angle changes from 0 to 30, which shows no statistically significant difference (P > 0.01). Conclusion This research initially obtained the relevant MRI data of the TT-TG distance from different knee angles between the Chinese patella dislocation patient group and control group. The study received a new criterion to evaluate the TT-TG of patients with patella dislocations when the knee angle is below 30 degrees. The knee flexion angles need to be considered to measure the TT-TG distance when comprehensively evaluating patellofemoral instability. The TT-TG distance gradually increases when the knee changes from flexion to extension. The difference of the TT-TG distances shows no statistically significant difference.

Evolving Roles of Optimal Medical Therapy and PCI in Chronic Coronary Syndrome Patients with Stable Angina: Introduction.

This Introduction sets the stage for 5 subsequent papers that will follow, and which describe several key features of the ISCHEMIA Trial in depth, including clinical outcomes, beginning with a detailed discussion by Dr. David L. Brown from Washington University, St. Louis, MO on the "importance of OMT in the management of CCS patients" and how the results of ISCHEMIA reinforce the findings of earlier strategy trials in CCS patients. Drs. Rasha Al-Lamee and Darrel Francis from Royal College of London, UK, will discuss the important topic of "how to assess quality of life improvement with revascularization in CCS patients with chronic angina and lessons learned the ORBITA trial, including the importance of unblinded vs. blinded trials". Drs. Kreton Mavromatis from Emory University, Atlanta, GA and Eric Bates from the University of Michigan, Ann Arbor, MI, will next discuss whether (and how) the "role of revascularization and, in particular, PCI in CCS patients has changed following the publication of the ISCHEMIA Trial", followed by a paper highlighting the important role of assessing myocardial ischemia and no obstructive coronary arteries (INOCA) in patients with CCS and why this represents both an under-diagnosed and under-treated cause of chronic angina, especially in women with suspected CAD. Finally, the concluding paper by Drs. Boden, Kaski, and Bernard Gersh from the Mayo Clinic, Rochester, MN, will summarize "the future of managing chronic stable angina and how best to synthesize recent clinical trials evidence with evolving CCS management guidelines".

Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

AimPrevious studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy.MethodsPatients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6–12 months after treatment, and intention-to-treat analysis was used.ResultsWe screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60–0.97) vs. 66% (95% CI 0.40–0.86), p = 0.47, at 6 months and 68% (95% CI 0.43–0.87) vs. 72% (95% CI 0.46–0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group.ConclusionG-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02154269].

Unblinded and Blinded N-of-1 Trials Versus Usual Care: A Randomized Controlled Trial to Increase Statin Uptake in Primary Care.

The aim was to assess whether an intervention incorporating a practicable open-label n-of-1 trial would lead to greater uptake of statin than usual care and comparable uptake to a closed-label gold-standard n-of-1 trial. We enrolled patients who had stopped or declined statins into a 3-arm trial (usual care, unblinded, and blinded n-of-1 intervention arms). Physicians advised participants randomized to usual care to take statin therapy to prevent cardiovascular disease. In both intervention arms, physicians delivered a theoretically informed informed intervention endorsing the value of experimenting with medication in n-of-1 trials to assess whether it caused side-effects. In these trials, participants alternated between 4 weeks of medication and no medication (unblinded arm) or randomly sorted active and placebo (blinded arm) and recorded symptoms and symptom attributions for 6 months. Thereafter, physicians discussed participants' symptom reports during active/inactive treatment periods and asked participants to resume statins if appropriate. Seventy-three were randomized to the intervention arms and 20 to the control group. Fifty-six of 73 (77%) attempted the n-of-1 experiment; 28/36 (78%) in the unblinded arm; and 28/37 (76%) in the blinded arm. Forty-three of 56 (77%) completed the 6-month experiment and received feedback from the physician; 20/28 (71%) in the unblinded arm and 23/28 (82%) in the blinded arm. Thirty-three of 76 (45%) people restarted statins in the n-of-1 arms compared with 4/20 (20%) in the control arm, difference 24% (95% CI, 5%-43%; P=0.041). There was no evidence this differed between blinded and unblinded arms, difference 2% (95% CI, -20% to 24%; P=0.86). Adverse events occurred at a similar rate on and off statin. In patients refusing or intolerant of statin, supporting experimentation with n-of-1 trials increases medication uptake compared with usual care. Alternating on-off medication in unblinded n-of-1 experiments appears as effective as a blinded experiment. URL: https://doi.org/10.1186/ISRCTN11142694; Unique identifier: ISRCTN11142694.

High-Fidelity Hyperspectral Snapshot of Physical World: System Architecture, Dataset and Model

It is extremely challenging to acquire high-fidelity video of physical world at high spectral, high spatial and high temporal resolution (H <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$^{3}$</tex-math></inline-formula> R) granularities simultaneously. Existing hyperspectral scanning cameras offer groundtruth with sufficient spatiospectral resolutions but largely lack temporal details; while recent hyperspectral snapshot cameras (e.g., CASSI, PMVIS) enable high temporal resolution acquisition but present inferior capacity to measure fine-grained spatiospectral components as groundtruth. This work builds a joint snapshot-scanning spectral system (JS <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$^{4}$</tex-math></inline-formula> ), by means of which the acquired low spatiospectral video-rate snapshots can be guided by synchronous-captured high spatiospectral groundtruth in the hyperspectral propagation. We first register the snapshot-scanning image pairs of the JS <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$^{4}$</tex-math></inline-formula> using a physical imaging model, and then generate a computational hyperspectral image light dataset (CHILD) having both video-rate snapshot and corresponding scanned groundtruth of a specific scene. Taking advantage of the CHILD, we later develop an end-to-end spectral propagation network (SPN) that applies the spectral guided filter and channel attention mechanism to restore rich, and high-fidelity hyperspectral measurement of the dynamic physical world from limited spatiospectral snapshot. The proposed SPN is evaluated extensively using non-blind, blind and semi-blind experiments. For the proposed CHILD and other abundant datasets, our SPN outperforms the state-of-the-art methods greatly.

Obtaining the Dimensions and Orientation of 2D Rectangular Flakes from Sectioning Experiments in Flake Composites

Recently, we developed and reported the statistical validity of two methods for determining the planar aspect ratios of two-dimensional (2D) rectangular flakes in composites from the statistics of intersection lengths: one method is based on the maximum intersection length, and the other on the average intersection length. In this work, we show that these methods are valid and robust not only for flakes having isotropic, random in-plane orientations, but for the more general situations of planar orientations ranging from unidirectional (misalignment angle ϵ=0), to partially aligned (0&lt;ϵ&lt;π/2), to flakes of isotropic, random-in-plane orientations (ϵ=π/2). We prove, by Monte Carlo simulations and by numerical sectioning experiments, the validity of the proposed methods for characterizing the extent of the partial alignment (the misalignment angle ϵ) of 2D rectangular flakes in composites, based again on the statistics of the intersection lengths; this information can be obtained from cross-sections of composite samples used in optical or electron microscopy or using tomographic imaging techniques. The performance of these techniques was tested using blind experiments in numerically sectioned composites which contained up to 106 individual flakes, and was found to be very good for a wide range of flake aspect ratios.