An Unguided, Computerized Cognitive Behavioral Therapy Intervention (TreadWill) in a Lower Middle-Income Country: Pragmatic Randomized Controlled Trial.

BACKGROUND: Globally, most individuals who are susceptible to depression do not receive adequate or timely treatment. Unguided computerized cognitive behavioral therapy (cCBT) has the potential to bridge this treatment gap. However, the real-world effectiveness of unguided cCBT interventions, particularly in low- and middle-income countries (LMICs), remains inconclusive. OBJECTIVE: In this study, we aimed to report the design and development of a new unguided cCBT-based multicomponent intervention, TreadWill, and its pragmatic evaluation. TreadWill was designed to be fully automated, engaging, easy to use, and accessible to LMICs. METHODS: To evaluate the effectiveness of TreadWill and the engagement level, we performed a double-blind, fully remote, and randomized controlled trial with 598 participants in India and analyzed the data using a completer's analysis. RESULTS: The users who completed at least half of the modules in TreadWill showed significant reduction in depression-related (P=.04) and anxiety-related (P=.02) symptoms compared with the waitlist control. Compared with a plain-text version with the same therapeutic content, the full-featured version of TreadWill showed significantly higher engagement (P=.01). CONCLUSIONS: Our study provides a new resource and evidence for the use of unguided cCBT as a scalable intervention in LMICs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03445598; https://clinicaltrials.gov/ct2/show/NCT03445598.

A Markovian influence graph formed from utility line outage data to mitigate large cascades.

We use observed transmission line outage data to make a Markovian influence graph that describes the probabili- ties of transitions between generations of cascading line outages. Each generation of a cascade consists of a single line outage or multiple line outages. The new influence graph defines a Markov chain and generalizes previous influence graphs by including multiple line outages as Markov chain states. The generalized influence graph can reproduce the distribution of cascade size in the utility data. In particular, it can estimate the probabilities of small, medium and large cascades. The influence graph has the key advantage of allowing the effect of mitigations to be analyzed and readily tested, which is not available from the observed data. We exploit the asymptotic properties of the Markov chain to find the lines most involved in large cascades and show how upgrades to these critical lines can reduce the probability of large cascades.

Wound healing activity of the ethanol root extract and polyphenolic rich fraction from Potentilla fulgens.

CONTEXT: Potentilla fulgens Wall. ex Hook (Rosaceae) is a potent medicinal plant of the Western Himalayas, where its roots are traditionally used by the local people of Uttaranchal (India) to treat wounds and tiger bites. OBJECTIVE: The present study scientifically evaluates the wound healing activity of P. fulgens ethanol root extract (EPF) and its ethyl acetate fraction (PFEA) on experimental rats. MATERIALS AND METHODS: Wounds were inflicted on animals by using both excision and incision models. The wounded animals were treated for 16 days with EPF (oral: 200-400 mg/kg and topical: 5-10% w/w) and PFEA (oral: 75 mg/kg; topical: 1.75% w/w). Various physical (wound contraction, epithelialization rate, tensile strength) and biochemical parameters (hydroxyproline, hexosamine, proteins, DNA) were examined during the study. Oxidant product (lipidperoxidase), antioxidant enzymes (catalase, superoxide-dismutase) and reduced glutathione were determined. Morphological and histopathological studies of the skin tissues were monitored. RESULTS: A significant (p < 0.05) wound healing property was observed when the animals were treated topically with EPF (10% w/w) and PFEA (1.75% w/w). A significantly (p < 0.05) increased in the levels of hydroxyproline, hexosamine, protein and DNA up to 59.22, 70.42, 61.01 and 60.00% was observed, respectively. This effect was further demonstrated by the morphological and histopathological representation, thus showing significant (p < 0.05) re-epethelialization on the healing area. EPF and PFEA also showed significant (p < 0.05) antioxidant activity. CONCLUSIONS: The present study provided the scientific evidence, where P. fulgens rich in polyphenolic components possess remarkable wound healing activities, thereby supporting the traditional claims.

Electrical stimulation: a novel therapeutic strategy to heal biological wounds.

Electrical stimulation (ES) has emerged as a powerful therapeutic modality for enhancing biological wound healing. This non-invasive technique utilizes low-level electrical currents to promote tissue regeneration and expedite the wound healing process. ES has been shown to accelerate wound closure, reduce inflammation, enhance angiogenesis, and modulate cell migration and proliferation through various mechanisms. The principle goal of wound management is the rapid recovery of the anatomical continuity of the skin, to prevent infections from the external environment and maintain homeostasis conditions inside. ES at the wound site is a compelling strategy for skin wound repair. Several ES applications are described in medical literature like AC, DC, and PC to improve cutaneous perfusion and accelerate wound healing. This review aimed to evaluate the primary factors and provides an overview of the potential benefits and mechanisms of ES in wound healing, and its ability to stimulate cellular responses, promote tissue regeneration, and improve overall healing outcomes. We also shed light on the application of ES which holds excellent promise as an adjunct therapy for various types of wounds, including chronic wounds, diabetic ulcers, and surgical incisions.

A Digital Single-Session Intervention (Project Engage) to Address Fear of Negative Evaluation Among College Students: Pilot Randomized Controlled Trial.

BACKGROUND: Increasingly, college science courses are transitioning from a traditional lecture format to active learning because students learn more and fail less frequently when they engage in their learning through activities and discussions in class. Fear of negative evaluation (FNE), defined as a student's sense of dread associated with being unfavorably evaluated while participating in a social situation, discourages undergraduates from participating in small group discussions, whole class discussions, and conversing one-on-one with instructors. OBJECTIVE: This study aims to evaluate the acceptability of a novel digital single-session intervention and to assess the feasibility of implementing it in a large enrollment college science course taught in an active learning way. METHODS: To equip undergraduates with skills to cope with FNE and bolster their confidence, clinical psychologists and biology education researchers developed Project Engage, a digital, self-guided single-session intervention for college students. It teaches students strategies for coping with FNE to bolster their confidence. Project Engage provides biologically informed psychoeducation, uses interactive elements for engagement, and helps generate a personalized action plan. We conducted a 2-armed randomized controlled trial to evaluate the acceptability and the preliminary effectiveness of Project Engage compared with an active control condition that provides information on available resources on the college campus. RESULTS: In a study of 282 upper-level physiology students, participants randomized to complete Project Engage reported a greater increase in overall confidence in engaging in small group discussions (P=.01) and whole class discussions (P<.001), but not in one-on-one interactions with instructors (P=.05), from baseline to immediately after intervention outcomes, compared with participants in an active control condition. Project Engage received a good acceptability rating (1.22 on a scale of -2 to +2) and had a high completion rate (>97%). CONCLUSIONS: This study provides a foundation for a freely available, easily accessible intervention to bolster student confidence for contributing in class. TRIAL REGISTRATION: OSF Registries osf.io/4ca68 http://osf.io/4ca68.

Serious Games Based on Cognitive Bias Modification and Learned Helplessness Paradigms for the Treatment of Depression: Design and Acceptability Study.

BACKGROUND: Depression is a debilitating mental health disorder, with a large treatment gap. Recent years have seen a surge in digital interventions to bridge this treatment gap. Most of these interventions are based on computerized cognitive behavioral therapy. Despite the efficacy of computerized cognitive behavioral therapy-based interventions, their uptake is low and dropout rates are high. Cognitive bias modification (CBM) paradigms provide a complementary approach to digital interventions for depression. However, interventions based on CBM paradigms have been reported to be repetitive and boring. OBJECTIVE: In this paper, we described the conceptualization, design, and acceptability of serious games based on CBM paradigms and the learned helplessness paradigm. METHODS: We searched the literature for CBM paradigms that were shown to be effective in reducing depressive symptoms. For each of the CBM paradigms, we ideated how to create a game so that the gameplay was engaging while the active therapeutic component remained unchanged. RESULTS: We developed 5 serious games based on the CBM paradigms and the learned helplessness paradigm. The games include various core elements of gamification, such as goals, challenges, feedback, rewards, progress, and fun. Overall, the games received positive acceptability ratings from 15 users. CONCLUSIONS: These games may help improve the effectiveness and engagement levels of computerized interventions for depression.

Effect of pooling family oral fluids on the probability of PRRSV RNA detection by RT-rtPCR.

Family oral fluids (FOFs) are an aggregate sample type shown to be a cost-efficient and convenient option for determining the porcine reproductive and respiratory syndrome virus (PRRSV) status of weaning age pigs. This study investigates the effect of pooling PRRSV-positive FOF samples with PRRSV-negative FOF samples at different levels (1/3, 1/5, 1/10, 1/20) on the probability of PRRSV RNA detection by reverse-transcription real-time polymerase chain reaction (RT-rtPCR). Mathematical models were built to assess how much the probability of RT-rtPCR PRRSV detection changed with increasing proportion of PRRSV-positive samples present within pools and how partially sampling a farrowing room influenced the probability of RT-rtPCR detection of PRRSV RNA in pooled samples at different prevalence scenarios. A general example of a guideline for FOF-based sampling under different prevalence scenarios to detect PRRSV RNA by RT-rtPCR with at least 95 % certainty is presented. At the sample level, the probability of detecting PRRSV RNA by RT-rtPCR decreased from 100 % to 87 %, 68 %, and 26 % when diluting up to 1/20 for PRRSV positive FOF having an initial Cycle threshold (Ct) below 34, between 34 and 36, or above 36, respectively. When PRRSV prevalence is near-zero (1 or 2 litters positive out of 56), the most cost-efficient farrowing room sampling strategy to detect PRRSV RNA with at least 95 % certainty was pooling FOF samples up to 1/10; at higher prevalence (≥ 3 of 56 litters positive), the most cost-efficient strategy was submitting samples in pools of 20. Subsampling a farrowing room for FOF pools was also demonstrated to be a valuable cost-saving strategy. Overall, based on the conditions of this study, pooling FOFs up to 1/20 is a valid option in situations of cost constraint and regardless of pooling level chosen, capturing as many litters as possible improves the probability of PRRSV detection.

Favorite Sites of a Persistent Random Walk.

We consider favorite (i.e., most visited) sites of a symmetric persistent random walk on ℤ , a discrete-time process typified by the correlation of its directional history. We show that the cardinality of the set of favorite sites is eventually at most three. This is a generalization of a result by Tóth for a simple random walk, used to partially prove a longstanding conjecture by Erdos and Róvósz. The original conjecture asserting that for the simple random walk on integers the cardinality of the set of favorite sites is eventually at most two was recently disproved by Ding and Shen.

Development and testing of a game-based digital intervention for working memory training in autism spectrum disorder.

Autism spectrum disorder (ASD) is prevalent globally, yet it lacks cost-effective treatment approaches. Deficits in executive functions occur frequently in autism spectrum disorder and present a target for intervention. Here we report the design and development of five smartphone-based games for training working memory in children with ASD. These open-source games, available free of cost to the community, were designed to match the behavioral preferences and sensorimotor abilities of children with ASD. We then conducted a preliminary trial to test the effectiveness of a month-long intervention using these games. Although we did not see a significant change in the working memory of all children with a month-long training, children who performed better on the games also showed more improvement in their working memory, suggesting that a longer intervention with the games might be useful in improving working memory. Using a Hindi translation of the autism treatment evaluation checklist, we also tested the collateral gains of the training in reducing autistic symptoms. We found no significant change in the autistic symptoms after the intervention. Further, there was no correlation between the change in the working memory and the change in the autistic symptoms.

Reusing the Past Difference Vectors in Differential Evolution-A Simple But Significant Improvement.

Differential evolution (DE) has established itself as a simple but efficient population-based, nonconvex optimization algorithm for continuous search spaces. Unlike the conventional real-coded genetic algorithms (GAs) and evolution strategies (ESs), DE uses a mandatory self-referential mutation for its population members, each of which are perturbed with the scaled difference(s) of the individuals from the current generation (iteration). These difference vectors determine the direction of the search moves for the individuals. However, unlike the better individuals, they are not retained in the elitist evolution cycle of DE. In this paper, we show that by archiving the most promising difference vectors from past generations and then by reusing them for generating offspring in the subsequent generations, we can strikingly improve the performance of DE. This strategy can be integrated with any classical or advanced DE variant with no serious overhead in time or space complexity. We demonstrate that when combined with the DE-based winners of the IEEE Congress on Evolutionary Computation (CEC) 2013, 2014, and 2017 competitions on real parameter optimization, the simple reuse strategy leads to a statistically significant performance improvement in the majority of test cases. We further showcase the efficacy of our proposal on a practical optimization problem concerning the design of circular antenna arrays with a prespecified radiation pattern.

Hospital-Wide Medication Reconciliation Program: Error Identification, Cost-Effectiveness, and Detecting High-Risk Individuals on Admission.

BACKGROUND: Medication reconciliation (MR) on admission has potential to reduce negative patient outcomes. The objectives of this prospective observational study were to 1) measure the impact a hospital-wide MR program has on home medication error identification at hospital admission, 2) demonstrate cost-effectiveness of this program, and 3) identify risk factors placing individual patients at higher risk for medication discrepancies. METHODS: Technicians obtained medication histories on adult patients admitted to the hospital that managed their own medications. Frequency and type of medication errors were recorded. Cost avoidance estimations were determined based on expected adverse drug event rates. Logistic regression analysis was used to test for associations between medication errors and patient characteristics. Results were considered significant when p-value was less than 0.05. RESULTS: The study included 817 patients. Technicians recorded a mean of 6.1 medication discrepancies per patient (SD ± 0.4) and took 28.5 minutes (SD ± 1.2 minutes) to complete a medication history. Omission, commission, and dosing/frequency errors occurred in 82%, 59%, and 50% of medication histories, respectively. We estimated cost avoidance of $210.33 per patient with this program. Female gender, age, and high alert/risk medication use were linked to an increase in the likelihood of occurrence of a medication discrepancy. CONCLUSION: This study validated the ability of a pharmacy technician to identify errors, demonstrated economic cost-effectiveness, provided new data on time to obtain a BPMH, and further identified factors that contribute to the occurrence of medication discrepancies. Potentially harmful medication discrepancies were identified frequently on admission. With further research, it may be possible to identify those at highest risk for home medication discrepancies upon admission.

Merging K-means with hierarchical clustering for identifying general-shaped groups.

Clustering partitions a dataset such that observations placed together in a group are similar but different from those in other groups. Hierarchical and K-means clustering are two approaches but have different strengths and weaknesses. For instance, hierarchical clustering identifies groups in a tree-like structure but suffers from computational complexity in large datasets while K-means clustering is efficient but designed to identify homogeneous spherically-shaped clusters. We present a hybrid non-parametric clustering approach that amalgamates the two methods to identify general-shaped clusters and that can be applied to larger datasets. Specifically, we first partition the dataset into spherical groups using K-means. We next merge these groups using hierarchical methods with a data-driven distance measure as a stopping criterion. Our proposal has the potential to reveal groups with general shapes and structure in a dataset. We demonstrate good performance on several simulated and real datasets.

Genetic and genomic perspective to understand the molecular pathogenesis of keratoconus.

Keratoconus (KC; Mendelian Inheritance in Man (OMIM) 14830) is a bilateral, progressive corneal defect affecting all ethnic groups around the world. It is the leading cause of corneal transplantation. The age of onset is at puberty, and the disorder is progressive until the 3 rd -4 th decade of life when it usually arrests. It is one of the major ocular problems with significant social and economic impacts as the disease affects young generation. Although genetic and environmental factors are associated with KC, but the precise etiology is still elusive. Results from complex segregation analysis suggests that genetic abnormalities may play an essential role in the susceptibility to KC. Due to genetic heterogeneity, a recent study revealed 17 different genomic loci identified in KC families by linkage mapping in various populations. The focus of this review is to provide a concise update on the current knowledge of the genetic basis of KC and genomic approaches to understand the disease pathogenesis.

Non-invasive fall risk assessment in community dwelling elderly with wireless inertial measurement units.

Falls are among the most serious accidents among the elderly leading to increased injuries, reduced functioning and mortality. In 2009, about 2.2 million nonfatal fall injuries were reported among the elderly population (CDC, 2010). In this study, eleven community dwelling elderly (aged 65-84 years) participated in fall risk assessment camp at sterling senior center organized by Northern Virginia Fall Prevention Coalition (NVFPC). Three custom made wireless inertial measurement units (IMUs) were attached on trunk and both shanks. All participants performed postural and locomotor tasks such as sit-to-stand (STS) and timed up and go (TUG). Temporal and kinematic parameters were obtained. Raw signals obtained were denoised using ensemble empirical mode decomposition and savistzky-golay filtering. The mean and standard deviation of TUG time and STS completion time for participants were found to be 11.3±6.6 sec and 3.58±2.07 sec respectively. The high variation in the result may be due to the use of assistive devices (i.e., cane and walker) by two participants. The objective of this study is to classify fall prone community dwelling individuals using non-invasive system. Four participants were classified as fall prone, three without fall risk and four were at potential risk based on their objective assessment and task performance. This system provides a platform for identifying fall prone individuals and may be used for early fall interventions among the elderly.

Effects of planar and non-planar driver-side mirrors on age-related discomfort-glare responses.

In this study, we evaluated subjective nighttime discomfort-glare responses on three different types of planar and non-planar driver-side mirrors on two age groups. Fifty-six individuals (28 young [18-35 years] and 28 old [65 years and over]) participated in this experiment. Subjective discomfort-glare rating scores on three different types of driver-side mirrors were assessed utilizing De Boer's rating scale in a controlled nighttime driving environment (laboratory ambient illuminant level-l lux with headlight turned off). Three driver-side mirrors included planar "flat mirror": radius of curvature 242650.92 mm, reflectivity 0.60114, and surface reflectance 0.60568; "curved mirror": radius of curvature 1433.3 mm, reflectivity 0.21652, and surface reflectance 0.58092; "blue mirror": radius of curvature 1957.1 mm, reflectivity 0.25356, and surface reflectance 0.54585. The results indicated that with the same glare level (as measured by angle of incidence and illuminance in front of the eyes), older adults reported worse feelings of glare than their younger counterparts. Furthermore, the results indicated that both young and older adults reported worse feelings of glare for planar driver-side mirror than non-planar driver-side mirrors. These results suggest that older adults' criterion of discomfort-glare is more sensitive than their younger counterparts, and importantly, the non-planar driver-side mirrors can be beneficial in terms of reducing nighttime discomfort-glare for both the young and the elderly.